of exercise-induced antidepressant-like effects, neurogenesis, as well as angiogenesis in the hippocampus [69, 87]. Additionally, VEGF polymorphism (VEGF2578C/A) causing low serum VEGF levels in humans may induce the development of treatment-resistant depression [88]. When VEGF and IGF-1 are injected into the brain, they show anti-depressant effects [89, 90]. Peripheral IGF-1 blocking prevents exercise-induced anti-depressant effects and hippocampal

Neurophysiological Effects of Exercise http://dx.doi.org/10.5772/64801 75

As acute and chronic exercise causes an increase in plasma endorphin levels, it is proposed that endorphins may play a role in the anti-depressant effects of exercise [7]. Though endorphins are related to positive mood and well-being, the role of endorphins in exercise is still controversial as there are studies showing increased peripheral endorphins do not affect the brain [7, 91]. Monoamines are neurotransmitters with anti-depressant effects, and it is thought they may mediate the effects of exercise [92]. It has been reported that exercise increases monoamine levels in different brain area. In rodents, altered serotonin levels and serotonin metabolism has been reported in different brain area such as striatum, hippocampus, hypothalamus, cerebral cortex and brain stem following acute and chronic exercise [93]. In clinical practice, serotonergic medications are used as anti-depressants and actually exercise may be as effective as these medications for mild and moderate depression [94]. As mentioned before, eCB system may contribute to exercise-induced antidepressant-like effects [95]. Indeed, exercise-induced increase in peripheral and central concentrations of eCBs and monoamines are thought to mediate the anti-depressant and

Regular exercise activates neurogenesis, angiogenesis, synaptogenesis and synaptic functions in the brain via a variety of neurobiological modulators, ensuring cognitive healing. As a result, it is thought that regular exercise may prevent or improve cognitive loss in both healthy elderly

In the normal ageing process, the neural plasticity of the brain reduces and this is accompanied by cognitive declines [2, 4]. The positive effects of exercise on the brain continue in elderly individuals though not as strongly as for young individuals. It has been shown that exercise exerts protective effects against cognitive decline and brain atrophy related to ageing. Kronenberg and colleagues reported that 3–9 months of exercise partially restored the reduced cell proliferation related to ageing and increased the number

Regular exercise reversed the age-related LTP decrease and it was accompanied by improved memory, increased hippocampal neurogenesis and increased BDNF levels in middle-aged rodents [97, 98]. Reduced BDNF and TrkB expression in the DG region was restored by 5 weeks [99] and 8 months [97] of forced treadmill exercise and by voluntary exercise [98] in middle-aged rats. This effect was in parallel with increased neurogenesis and improved cognitive functions [97–99]. Similarly, 8 weeks of treadmill exercise restored reduced NGF levels in the hippocampus of elderly rats [100]. Tsai et al. showed that 1 year

neurogenesis showing the importance of IGF-1 [63, 89].

anxiolytic effects of exercise.

people and those with risk of dementia.

**3.3. Exercise and ageing**

of mature cells [96].

Serotonin, dopamine and norepinephrine are the central neurotransmitters known as monoamines. Studies demonstrated that monoamines can regulate synaptic plasticity, neuronal survival and mood. It is suggested that monoamines may have a role in the exercise-induced positive effects on brain. Long-term exercise induces significant elevation of norepinephrine and serotonin levels in different brain areas, compared to the sedentary controls [78]. Klempin et al. studied tryptophan hydroxylase-2-deficient mice and investigated the neurogenic effects of serotonin deficiency [79]. The researchers found that basal neurogenesis in the hippocampus of these animals was normal; however, they showed exercise-induced neurogenesis to be reduced. These results indicate that the serotonergic system plays an important role in the effect of exercise on neuroplasticity.

#### **3.2. Exercise and mood**

Though chronic and uncontrolled stress has a negative effect on mood, it is understood that differences in the type of stress may change results [80]. For example, voluntary exercise is a stress factor (physical stress) due to activation of the sympathetic nervous system and hypothalamic-pituitary-adrenal axis [81]. However, exercise also causes release of growth hormone and various neurotrophic factors different to other stress factors such as psychological stress. Additionally, in those who exercise the transformation of the stress hormone cortisol to the inactive form of cortisone is higher and this situation is not observed with psychological stress. Finally, as exercise can be ceased whenever the person desires, it is a different to other types of stress and causes different results [7].

Clinical studies of patient with mild-to-moderate levels of depression have shown that exercise reduces depressive symptoms [82]. Additionally, animal studies showed that wheel-running activity had anti-depressant-like effects on learned helplessness, forced swim test and tail suspension tests [83]. Though the underlying mechanism responsible for the anti-depressantlike effects of exercise is not fully known, neurotrophic factors and neurotransmitter systems may provide significant contribution. For example, BDNF, IGF-1 and VEGF are thought to regulate anti-depressant-like effects of exercise [77]. Of these, BDNF may be more important than the others, because depression is related to BDNF deficiency of both the circulation and CNS. In depressive patients, peripheral BDNF levels are at lower levels compared to control [84]. Moreover, postmortem studies have shown low levels of BDNF in the cortical and hippocampal areas of the brain [85]. Studies using a variety of behaviour models have confirmed the effect of BDNF on mood by showing anti-depressant and anxiolytic effect of recombinant BDNF administration into the brain [86]. More importantly, reduced BDNF levels and depressive behaviour associated with acute and chronic stress are successfully prevented by exercise [77].

The reduction in hippocampal VEGF expression during chronic stress in rodents has shown that VEGF may be related to depression [77]. Peripheral blocking of VEGF exerts prevention of exercise-induced antidepressant-like effects, neurogenesis, as well as angiogenesis in the hippocampus [69, 87]. Additionally, VEGF polymorphism (VEGF2578C/A) causing low serum VEGF levels in humans may induce the development of treatment-resistant depression [88]. When VEGF and IGF-1 are injected into the brain, they show anti-depressant effects [89, 90]. Peripheral IGF-1 blocking prevents exercise-induced anti-depressant effects and hippocampal neurogenesis showing the importance of IGF-1 [63, 89].

As acute and chronic exercise causes an increase in plasma endorphin levels, it is proposed that endorphins may play a role in the anti-depressant effects of exercise [7]. Though endorphins are related to positive mood and well-being, the role of endorphins in exercise is still controversial as there are studies showing increased peripheral endorphins do not affect the brain [7, 91]. Monoamines are neurotransmitters with anti-depressant effects, and it is thought they may mediate the effects of exercise [92]. It has been reported that exercise increases monoamine levels in different brain area. In rodents, altered serotonin levels and serotonin metabolism has been reported in different brain area such as striatum, hippocampus, hypothalamus, cerebral cortex and brain stem following acute and chronic exercise [93]. In clinical practice, serotonergic medications are used as anti-depressants and actually exercise may be as effective as these medications for mild and moderate depression [94]. As mentioned before, eCB system may contribute to exercise-induced antidepressant-like effects [95]. Indeed, exercise-induced increase in peripheral and central concentrations of eCBs and monoamines are thought to mediate the anti-depressant and anxiolytic effects of exercise.

#### **3.3. Exercise and ageing**

for CB1R in the hippocampus and the levels of the endocannabinoid anandamide [76]. These alterations seem to be necessary for exercise-induced neuroplasticity in the hippocampus and are suggested to be mediators of the anti-depressant and anxiolytic

Serotonin, dopamine and norepinephrine are the central neurotransmitters known as monoamines. Studies demonstrated that monoamines can regulate synaptic plasticity, neuronal survival and mood. It is suggested that monoamines may have a role in the exercise-induced positive effects on brain. Long-term exercise induces significant elevation of norepinephrine and serotonin levels in different brain areas, compared to the sedentary controls [78]. Klempin et al. studied tryptophan hydroxylase-2-deficient mice and investigated the neurogenic effects of serotonin deficiency [79]. The researchers found that basal neurogenesis in the hippocampus of these animals was normal; however, they showed exercise-induced neurogenesis to be reduced. These results indicate that the serotonergic system plays an important role in the

Though chronic and uncontrolled stress has a negative effect on mood, it is understood that differences in the type of stress may change results [80]. For example, voluntary exercise is a stress factor (physical stress) due to activation of the sympathetic nervous system and hypothalamic-pituitary-adrenal axis [81]. However, exercise also causes release of growth hormone and various neurotrophic factors different to other stress factors such as psychological stress. Additionally, in those who exercise the transformation of the stress hormone cortisol to the inactive form of cortisone is higher and this situation is not observed with psychological stress. Finally, as exercise can be ceased whenever the person desires, it is a different to other types

Clinical studies of patient with mild-to-moderate levels of depression have shown that exercise reduces depressive symptoms [82]. Additionally, animal studies showed that wheel-running activity had anti-depressant-like effects on learned helplessness, forced swim test and tail suspension tests [83]. Though the underlying mechanism responsible for the anti-depressantlike effects of exercise is not fully known, neurotrophic factors and neurotransmitter systems may provide significant contribution. For example, BDNF, IGF-1 and VEGF are thought to regulate anti-depressant-like effects of exercise [77]. Of these, BDNF may be more important than the others, because depression is related to BDNF deficiency of both the circulation and CNS. In depressive patients, peripheral BDNF levels are at lower levels compared to control [84]. Moreover, postmortem studies have shown low levels of BDNF in the cortical and hippocampal areas of the brain [85]. Studies using a variety of behaviour models have confirmed the effect of BDNF on mood by showing anti-depressant and anxiolytic effect of recombinant BDNF administration into the brain [86]. More importantly, reduced BDNF levels and depressive behaviour associated with acute and chronic stress are successfully prevented

The reduction in hippocampal VEGF expression during chronic stress in rodents has shown that VEGF may be related to depression [77]. Peripheral blocking of VEGF exerts prevention

effects of exercise [77].

74 Fitness Medicine

effect of exercise on neuroplasticity.

of stress and causes different results [7].

**3.2. Exercise and mood**

by exercise [77].

Regular exercise activates neurogenesis, angiogenesis, synaptogenesis and synaptic functions in the brain via a variety of neurobiological modulators, ensuring cognitive healing. As a result, it is thought that regular exercise may prevent or improve cognitive loss in both healthy elderly people and those with risk of dementia.

In the normal ageing process, the neural plasticity of the brain reduces and this is accompanied by cognitive declines [2, 4]. The positive effects of exercise on the brain continue in elderly individuals though not as strongly as for young individuals. It has been shown that exercise exerts protective effects against cognitive decline and brain atrophy related to ageing. Kronenberg and colleagues reported that 3–9 months of exercise partially restored the reduced cell proliferation related to ageing and increased the number of mature cells [96].

Regular exercise reversed the age-related LTP decrease and it was accompanied by improved memory, increased hippocampal neurogenesis and increased BDNF levels in middle-aged rodents [97, 98]. Reduced BDNF and TrkB expression in the DG region was restored by 5 weeks [99] and 8 months [97] of forced treadmill exercise and by voluntary exercise [98] in middle-aged rats. This effect was in parallel with increased neurogenesis and improved cognitive functions [97–99]. Similarly, 8 weeks of treadmill exercise restored reduced NGF levels in the hippocampus of elderly rats [100]. Tsai et al. showed that 1 year of regular resistance exercise increased IGF-1 levels and improved cognitive functions in the elderly [55].

*3.4.2. Parkinson's disease*

and PD patients [115].

*3.4.3. Huntington's Disease*

exercise in HD patients is needed.

**3.5. Effective type, duration and intensity of exercise**

PD develops as a result of degeneration of dopaminergic neurons with projection from the SN pars compacta to the striatum and causes severe motor symptoms such as weakened motor activity control, akinesia, tremor and rigidity. Additionally, non-motor symptoms such as cognitive reduction, olfactory dysfunction, anxiety and depression may be observed in these patients [4, 6]. In a variety of rodent PD models, it has been shown that exercise may be beneficial in improving some neuropathological and behavioural defects [4, 6]. It has been reported that 4 weeks of exercise increases the trophic factor levels and cell proliferation rate in the striatum and additionally exerts a protective effect on tyrosine hydroxylase positive neurons in the striatum and SN [112]. Clinical studies of PD patients have shown that physical activity ensured improvements in postural stability, balance and cognitive functions [113, 114]. Even more, exercise provided attenuation of depression frequently observed in both AD

Neurophysiological Effects of Exercise http://dx.doi.org/10.5772/64801 77

HD is a progressive neurodegenerative disease caused by a genetic mutation of HD gene and characterized by neuron death in the striatum mainly, but also in some regions of the cortex and hippocampus. The most significant symptoms of HD are loss of coordination of voluntary movement, bradykinesia and rigidity. Reduced cognitive capacity observed in these patients causes progressive severe dementia over time [4, 6]. Studies on different transgenic mice models such as R6/1 HD, R6/2 HD and N171-82Q HD have shown that running wheel activity does not increase BDNF level or stimulate neurogenesis in the hippocampus [116, 117]. Nevertheless, exercise delays HD symptoms and improves cognition in similar study models [118]. The cognitive improvement caused by running in HD transgenic mice does not appear to be due to increased neurogenesis, but rather is due to structural remodelling of existing neurons in the hippocampus. Human studies have provided contradictory results. For example, Altschuler reported there was no recovery of the initiation or progression of HD symptoms in a semi-professional marathon runner [119]. On the contrary, in another study of HD patients undergoing 9 months of multidisciplinary rehabilitation, including exercise, an increase in grey matter volume in the right caudate region and bilateral dorsolateral prefrontal cortex is reported in addition to significantly improved word learning and memory performance [120]. Contradictory findings suggest that more detailed investigation into the effects of

Aerobic exercise basically has positive effects on cardiovascular and metabolic functions, while resistance exercise is very beneficial for muscle strength and bone density. As mentioned above, there is much scientific proof of the positive effects of exercise on neurologic functions. Studies have shown that both exercise types have similar positive effects on neuroplasticity. Cassilhas and colleagues in a study comparing the effects of aerobic and resistance exercise found that both types of exercise produced similar improvements in learning and spatial memory after an 8-week training period. However, as aerobic exercise causes an increase in IGF-1, BDNF,

Human studies have identified a positive correlation between the incidence, duration and distance of daily walking activity by the elderly and the size of the hippocampus [101]. A similar study investigated the correlation between cardiovascular fitness and hippocampus volume in the elderly and showed a positive correlation between aerobic fitness (VO2 peak) and right and left hippocampus size [102]. Elderly individuals participating in a 6-month aerobic exercise programme (60–70% of maximal heart rate, 3 times per week, 1 h) were observed to have increased grey matter and white matter volumes in the brain [103]. Cognition studies have found that cognitive functions in elderly individuals completing 3 h or more of aerobic exercise per week for at least the last 2 years were better than in sedentary individuals [104]. Another study observed that sedentary elderly individuals who participated in a 24-week aerobic exercise programme had improved cognitive functions [105]. Taken together, these results suggest that exercise is a good strategy to improve age-related brain atrophy and cognitive decline.

#### **3.4. Exercise and neurodegenerative diseases**

Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD), show general properties of progressive loss of neurons. Indeed, neuronal degeneration predominantly affects different neuron groups and it is well documented that dopaminergic neurons in PD, striatal GABAergic neurons in HD and cortical and hippocampal cholinergic neurons in AD are progressively degenerated during diseases. Certain degrees of learning and memory loss are associated with progressive structural and functional deterioration of neurons in all neurodegenerative diseases [4, 6]. As the exercise stimulates neurogenesis and improves cognition in both young and old individuals, it is reasonable to think that it may have protective effect against neurodegenerative diseases.

#### *3.4.1. Alzheimer's Disease*

Pathologically, AD is characterized by acetylcholine depletion, amyloid (or senile) plaque formation, neuronal apoptosis in the cortex and hippocampus as well as brain atrophy. Additionally, decreased cognitive functions, memory loss, behavioural changes and dementia are the other characteristics of the disease [106]. In a number of AD mice models, running was observed to improve neurogenesis and cognitive functions. For example, short-term running improved cognitive functions of elderly Tg2576 mice [107], and 5 month long-term voluntary running not only prevented plaque formation in the frontal cortex and hippocampus, but also improved spatial learning in TgCRND8 D mice [108]. Similar results were obtained from APP/PS1 double transgenic AD mouse model with treadmill exercise improving learning, memory and LTP and providing amelioration of neuropathological characteristics of the disease [109]. In humans with high risk of AD, increased physical activity has been shown to reduce hippocampal atrophy [110, 111].

#### *3.4.2. Parkinson's disease*

of regular resistance exercise increased IGF-1 levels and improved cognitive functions in

Human studies have identified a positive correlation between the incidence, duration and distance of daily walking activity by the elderly and the size of the hippocampus [101]. A similar study investigated the correlation between cardiovascular fitness and hippocampus volume in the elderly and showed a positive correlation between aerobic fitness (VO2 peak) and right and left hippocampus size [102]. Elderly individuals participating in a 6-month aerobic exercise programme (60–70% of maximal heart rate, 3 times per week, 1 h) were observed to have increased grey matter and white matter volumes in the brain [103]. Cognition studies have found that cognitive functions in elderly individuals completing 3 h or more of aerobic exercise per week for at least the last 2 years were better than in sedentary individuals [104]. Another study observed that sedentary elderly individuals who participated in a 24-week aerobic exercise programme had improved cognitive functions [105]. Taken together, these results suggest that exercise is a good

Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD), show general properties of progressive loss of neurons. Indeed, neuronal degeneration predominantly affects different neuron groups and it is well documented that dopaminergic neurons in PD, striatal GABAergic neurons in HD and cortical and hippocampal cholinergic neurons in AD are progressively degenerated during diseases. Certain degrees of learning and memory loss are associated with progressive structural and functional deterioration of neurons in all neurodegenerative diseases [4, 6]. As the exercise stimulates neurogenesis and improves cognition in both young and old individuals, it is reasonable to think that it may have protective effect

Pathologically, AD is characterized by acetylcholine depletion, amyloid (or senile) plaque formation, neuronal apoptosis in the cortex and hippocampus as well as brain atrophy. Additionally, decreased cognitive functions, memory loss, behavioural changes and dementia are the other characteristics of the disease [106]. In a number of AD mice models, running was observed to improve neurogenesis and cognitive functions. For example, short-term running improved cognitive functions of elderly Tg2576 mice [107], and 5 month long-term voluntary running not only prevented plaque formation in the frontal cortex and hippocampus, but also improved spatial learning in TgCRND8 D mice [108]. Similar results were obtained from APP/PS1 double transgenic AD mouse model with treadmill exercise improving learning, memory and LTP and providing amelioration of neuropathological characteristics of the disease [109]. In humans with high risk of AD, increased physical activity has been shown to reduce hippocampal atrophy [110, 111].

strategy to improve age-related brain atrophy and cognitive decline.

**3.4. Exercise and neurodegenerative diseases**

against neurodegenerative diseases.

*3.4.1. Alzheimer's Disease*

the elderly [55].

76 Fitness Medicine

PD develops as a result of degeneration of dopaminergic neurons with projection from the SN pars compacta to the striatum and causes severe motor symptoms such as weakened motor activity control, akinesia, tremor and rigidity. Additionally, non-motor symptoms such as cognitive reduction, olfactory dysfunction, anxiety and depression may be observed in these patients [4, 6]. In a variety of rodent PD models, it has been shown that exercise may be beneficial in improving some neuropathological and behavioural defects [4, 6]. It has been reported that 4 weeks of exercise increases the trophic factor levels and cell proliferation rate in the striatum and additionally exerts a protective effect on tyrosine hydroxylase positive neurons in the striatum and SN [112]. Clinical studies of PD patients have shown that physical activity ensured improvements in postural stability, balance and cognitive functions [113, 114]. Even more, exercise provided attenuation of depression frequently observed in both AD and PD patients [115].

#### *3.4.3. Huntington's Disease*

HD is a progressive neurodegenerative disease caused by a genetic mutation of HD gene and characterized by neuron death in the striatum mainly, but also in some regions of the cortex and hippocampus. The most significant symptoms of HD are loss of coordination of voluntary movement, bradykinesia and rigidity. Reduced cognitive capacity observed in these patients causes progressive severe dementia over time [4, 6]. Studies on different transgenic mice models such as R6/1 HD, R6/2 HD and N171-82Q HD have shown that running wheel activity does not increase BDNF level or stimulate neurogenesis in the hippocampus [116, 117]. Nevertheless, exercise delays HD symptoms and improves cognition in similar study models [118]. The cognitive improvement caused by running in HD transgenic mice does not appear to be due to increased neurogenesis, but rather is due to structural remodelling of existing neurons in the hippocampus. Human studies have provided contradictory results. For example, Altschuler reported there was no recovery of the initiation or progression of HD symptoms in a semi-professional marathon runner [119]. On the contrary, in another study of HD patients undergoing 9 months of multidisciplinary rehabilitation, including exercise, an increase in grey matter volume in the right caudate region and bilateral dorsolateral prefrontal cortex is reported in addition to significantly improved word learning and memory performance [120]. Contradictory findings suggest that more detailed investigation into the effects of exercise in HD patients is needed.

#### **3.5. Effective type, duration and intensity of exercise**

Aerobic exercise basically has positive effects on cardiovascular and metabolic functions, while resistance exercise is very beneficial for muscle strength and bone density. As mentioned above, there is much scientific proof of the positive effects of exercise on neurologic functions. Studies have shown that both exercise types have similar positive effects on neuroplasticity. Cassilhas and colleagues in a study comparing the effects of aerobic and resistance exercise found that both types of exercise produced similar improvements in learning and spatial memory after an 8-week training period. However, as aerobic exercise causes an increase in IGF-1, BDNF, TrkB and β-CaMKII (calcium/calmodulin-dependent kinase II] in the hippocampus, resistance exercise caused an increase in peripheral and hippocampal IGF-1, IGF-1R and AKT. According to the results of this study, aerobic and resistance exercise produces similar positive effects on learning and spatial memory by using different molecular mechanisms [121].

effective, low-cost and low-tech method for successful ageing, and therefore, it has a great potential to prevent or reduce age-related cognitive decline. Neurologically to ensure the optimum benefit from exercise, regular, mild-moderate intensity of the aerobic or resistance exercise appears to be appropriate, while it is recommended to avoid exhaustive type of

Neurophysiological Effects of Exercise http://dx.doi.org/10.5772/64801 79

exercise.

**Author details**

**References**

Selma Cırrık1\* and Gulay Hacioglu2

10.1155/2016/3583956.

10.1007/7854\_2012\_220.

Sports Med Open. 2015;1(1):35.

\*Address all correspondence to<EMAIL_ADDRESS>
1 Department of Physiology, Medical Faculty, Ordu University, Ordu, Turkey

2 Department of Physiology, Medical Faculty, Giresun University, Giresun, Turkey

[1] Ross M.D., Malone E., Florida-James G. Vascular ageing and exercise: focus on cellular reparative processes. Oxid Med Cell Longev. 2016;2016:3583956. doi:

[2] Brown W.M., Davison G.W., McClean C.M., Murphy M.H. A systematic review of the acute effects of exercise on immune and inflammatory indices in untrained adults.

[3] Vivar C., Potter M.C., van Praag H. All about running: synaptic plasticity, growth factors and adult hippocampal neurogenesis. Curr Top Behav Neurosci. 2013;15:189–210. doi:

[4] Yau S.Y., Gil-Mohapel J., Christie B.R., So K.F. Physical exercise-induced adult neurogenesis: a good strategy to prevent cognitive decline in neurodegenerative diseases?

[5] Cassilhas R.C., Tufik S., de Mello M.T. Physical exercise, neuroplasticity, spatial learning and memory. Cell Mol Life Sci. 2016;73(5):975–983. doi:10.1007/s00018-015-2102-0.

[6] van Praag H. Neurogenesis and exercise: past and future directions. Neuromol Med.

[7] Heijnen S., Hommel B., Kibele A., Colzato L.S. Neuromodulation of aerobic exercise-a

Biomed Res Int. 2014;2014:403120. doi:10.1155/2014/403120.

review. Front Psychol. 2016;6:1890. doi:10.3389/fpsyg.2015.01890.

2008;10(2):128–140. doi:10.1007/s12017-008-8028-z.

Molteni and colleagues investigated the time-dependent changes of the gene expression in the hippocampus induced by acute and chronic (3, 7 and 28 days] voluntary running wheel activity [73]. The researchers found that BDNF expression increased with all exercise durations and reported that BDNF played a central role in exercise-induced brain plasticity. Similarly, the CaM-K signal system increased with both acute exercise and chronic exercise; however, they reported that the MAP-K/ERK system was activated by long-term exercise.

When the effect of exercise types with different intensities is examined, mild-moderate intensity exercise seems to be more beneficial to the brain, while exhaustive exercise appears to be destructive. For example, Soya and colleagues investigated the effects of acute exercise (30 min, treadmill) at different intensities on the BDNF expression in the hippocampus in rats and showed that mild running (15 m/min) increased BDNF mRNA and protein levels [122]. Running at faster speeds (20 m/min) increases serum corticosterone levels along with only BNDF mRNA levels in the hippocampus, while causing a reduction in protein levels. The researchers stated that low-intensity exercise with minimum stress levels was more beneficial to the hippocampus. Another study investigated the effect of mild and intense treadmill exercise on cognitive function after traumatic brain injury in rats, and showed that 2 weeks of mild exercise increased hippocampal BDNF expression and improved cognitive functions [123]. In another study, Li and colleagues investigated the effects of exhaustive exercise and showed that different intensities of acute exhaustive exercise cause neuronal cell apoptosis in rats. From these results, it is understood that exhaustive exercise is not beneficial to the hippocampus and may in fact have a destructive effect [124].

#### **4. Conclusion**

The beneficial effects of exercise are most likely the result of a combination of increased number and maturation of newborn cells, modifications in synaptic plasticity and spine density and enhanced angiogenesis in the hippocampus. The most pronounced changes induced by exercise are observed in the DG subfield within the hippocampus. Exercise-induced increase in hippocampal neuroplasticity appears to be mediated by a variety of neurotrophic and angiogenic factors and neurotransmitter systems. Changes in hippocampus morphology and chemistry may mediate beneficial effects of exercise, such as improved learning and memory, anti-depressant-like and anxiolytic effects, reduced cognitive decline related to ageing and delay/reduction in symptoms of neurodegenerative disease.

Although further research is needed to understand the cellular mechanism responsible for the effects of exercise on the brain, it is clear that exercise could be used to maintain and improve cognitive function throughout the lifespan. It should be also noted that exercise is the most effective, low-cost and low-tech method for successful ageing, and therefore, it has a great potential to prevent or reduce age-related cognitive decline. Neurologically to ensure the optimum benefit from exercise, regular, mild-moderate intensity of the aerobic or resistance exercise appears to be appropriate, while it is recommended to avoid exhaustive type of exercise.

#### **Author details**

TrkB and β-CaMKII (calcium/calmodulin-dependent kinase II] in the hippocampus, resistance exercise caused an increase in peripheral and hippocampal IGF-1, IGF-1R and AKT. According to the results of this study, aerobic and resistance exercise produces similar positive effects on

Molteni and colleagues investigated the time-dependent changes of the gene expression in the hippocampus induced by acute and chronic (3, 7 and 28 days] voluntary running wheel activity [73]. The researchers found that BDNF expression increased with all exercise durations and reported that BDNF played a central role in exercise-induced brain plasticity. Similarly, the CaM-K signal system increased with both acute exercise and chronic exercise; however, they reported that the MAP-K/ERK system was activated

When the effect of exercise types with different intensities is examined, mild-moderate intensity exercise seems to be more beneficial to the brain, while exhaustive exercise appears to be destructive. For example, Soya and colleagues investigated the effects of acute exercise (30 min, treadmill) at different intensities on the BDNF expression in the hippocampus in rats and showed that mild running (15 m/min) increased BDNF mRNA and protein levels [122]. Running at faster speeds (20 m/min) increases serum corticosterone levels along with only BNDF mRNA levels in the hippocampus, while causing a reduction in protein levels. The researchers stated that low-intensity exercise with minimum stress levels was more beneficial to the hippocampus. Another study investigated the effect of mild and intense treadmill exercise on cognitive function after traumatic brain injury in rats, and showed that 2 weeks of mild exercise increased hippocampal BDNF expression and improved cognitive functions [123]. In another study, Li and colleagues investigated the effects of exhaustive exercise and showed that different intensities of acute exhaustive exercise cause neuronal cell apoptosis in rats. From these results, it is understood that exhaustive exercise is not beneficial to the

The beneficial effects of exercise are most likely the result of a combination of increased number and maturation of newborn cells, modifications in synaptic plasticity and spine density and enhanced angiogenesis in the hippocampus. The most pronounced changes induced by exercise are observed in the DG subfield within the hippocampus. Exercise-induced increase in hippocampal neuroplasticity appears to be mediated by a variety of neurotrophic and angiogenic factors and neurotransmitter systems. Changes in hippocampus morphology and chemistry may mediate beneficial effects of exercise, such as improved learning and memory, anti-depressant-like and anxiolytic effects, reduced cognitive decline related to ageing and

Although further research is needed to understand the cellular mechanism responsible for the effects of exercise on the brain, it is clear that exercise could be used to maintain and improve cognitive function throughout the lifespan. It should be also noted that exercise is the most

learning and spatial memory by using different molecular mechanisms [121].

hippocampus and may in fact have a destructive effect [124].

delay/reduction in symptoms of neurodegenerative disease.

by long-term exercise.

78 Fitness Medicine

**4. Conclusion**

Selma Cırrık1\* and Gulay Hacioglu2

\*Address all correspondence to<EMAIL_ADDRESS>
1 Department of Physiology, Medical Faculty, Ordu University, Ordu, Turkey

2 Department of Physiology, Medical Faculty, Giresun University, Giresun, Turkey

#### **References**

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**Chapter 5**

**Exercise for Hypertension**

Tortosa-Martínez Juan and Cortell-Tormo Juan Manuel

http://dx.doi.org/10.5772/65035

**Abstract**

cise, lifestyle

**1. Introduction**

Chulvi-Medrano Iván, Sanchis-Cervera José,

Tortosa-Martínez Juan and Cortell-Tormo Juan Manuel

Chulvi-Medrano Iván, Sanchis-Cervera José,

Additional information is available at the end of the chapter

the gap between theory and practice.

**Provisional chapterExercise for Hypertension**

High blood pressure (HBP) does not cause discomfort but still, you need to take care of and treat it. Otherwise, over time, it can damage the heart, kidneys, brain, and eyes. Lifestyle changes are essential in HBP, and physical activity is a parameter of great influence. In order to achieve the benefits derived from physical activity, it must be adequately prescribed, an aspect that will be developed in this chapter. The first section addresses the physiopathology of hypertension, with special interest in the pathological mechanisms that may induce hypertension, devices for monitoring blood pressure (BP), and an overview of the particularities that present hypertension in the presence of other pathologies and over the life span. Second section focuses on exercise prescription for hypertensive people, exploring each type of exercise that has been proved to be effective. We discuss for each type of exercise, the benefits, mechanisms involved in these benefits, the appropriate dose of exercise, and other methodological considerations including risk management issues. We conclude with a clinical case study. A detailed exercise training program will be developed for this particular case study in order to try to bridge

**Keywords:** primary hypertension, blood pressure, resistance training, aerobic exer‐

High blood pressure (HBP) is the greatest public health problem worldwide because of its high prevalence and because it is associated with increased cardiovascular and renal compli‐ cations. In the year 2000, hypertension in the adult population stood about 26.4%. Projected calculations for 2025 estimate the prevalence at 29.0%. In absolute terms worldwide, this

medium, provided the original work is properly cited.

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Additional information is available at the end of the chapter

#### **Chapter 5**

## **Exercise for Hypertension Provisional chapterExercise for Hypertension**

Chulvi-Medrano Iván, Sanchis-Cervera José, Tortosa-Martínez Juan and Cortell-Tormo Juan Manuel Chulvi-Medrano Iván, Sanchis-Cervera José, Tortosa-Martínez Juan and Cortell-Tormo Juan Manuel Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/65035

#### **Abstract**

High blood pressure (HBP) does not cause discomfort but still, you need to take care of and treat it. Otherwise, over time, it can damage the heart, kidneys, brain, and eyes. Lifestyle changes are essential in HBP, and physical activity is a parameter of great influence. In order to achieve the benefits derived from physical activity, it must be adequately prescribed, an aspect that will be developed in this chapter. The first section addresses the physiopathology of hypertension, with special interest in the pathological mechanisms that may induce hypertension, devices for monitoring blood pressure (BP), and an overview of the particularities that present hypertension in the presence of other pathologies and over the life span. Second section focuses on exercise prescription for hypertensive people, exploring each type of exercise that has been proved to be effective. We discuss for each type of exercise, the benefits, mechanisms involved in these benefits, the appropriate dose of exercise, and other methodological considerations including risk management issues. We conclude with a clinical case study. A detailed exercise training program will be developed for this particular case study in order to try to bridge the gap between theory and practice.

**Keywords:** primary hypertension, blood pressure, resistance training, aerobic exer‐ cise, lifestyle

#### **1. Introduction**

High blood pressure (HBP) is the greatest public health problem worldwide because of its high prevalence and because it is associated with increased cardiovascular and renal compli‐ cations. In the year 2000, hypertension in the adult population stood about 26.4%. Projected calculations for 2025 estimate the prevalence at 29.0%. In absolute terms worldwide, this

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

increase will go from 972 million hypertensives in 2000 to 1,560,000,000 in 2025, representing a raise of approximately 60% [1].

and maximize the benefits of exercise safely, professionals should have updated guidelines for prescribing exercise for hypertension. These guidelines should be based on scientific evidence and provide precise practical information about how to design, implement, and control a

Exercise for Hypertension http://dx.doi.org/10.5772/65035 93

From a clinical standpoint, the influence of genetics in hypertension is determined by a familial aggregation, so that the prevalence increases among relatives of first degree. Besides this clinical observation, knowledge of the genes involved in the development of hypertension is scarce. It seems clear that genetic determinants can be modified by environmental ones, so that the blood pressure or the resulting phenotype depends on the interaction of both factors. Genotypic and phenotypic research will be of great importance in the future as it may be able to help develop personalized treatments and prevention programs based on these findings [3–

The main factors related to the development of hypertension are linked to the progress and changes in lifestyle and diet. The mechanisms by which these environmental determinants increase blood pressure and promote the development of cardiovascular disease are not fully clarified but it seems that a high caloric intake and decreased energy expenditure produce

*1. Sympathetic overactivity*. It is characterized by an imbalance between sympathetic and parasympathetic activity. Sympathetic activation may be caused by a direct stimulus by chronic stress, high caloric intake, obesity, and physical inactivity among others. 2. *Renin-angiotensin system (RAS)*. The renin‐angiotensin system is undoubtedly mainly responsible for the development of vascular disease and one of the main focuses of therapeutic care. Angiotensin II is the main effector system with specific receptors at different levels that promote vasocon‐ striction and fluid retention, the latter thanks to the stimulation of adrenal aldosterone secretion as well as inflammatory, proaggregatory, and prothrombotic reactions. 3. *Dysfunction and endothelial injury*. The endothelium plays a fundamental role in vascular pathophysiology alterations observed in hypertension. Cardiovascular complications include both dysfunction and damage in the endothelial cell layer. In the latter case, the most plausible hypothesis is the inability of predisposed individuals to repair endothelial cell damage that occurs in normal circumstances, mainly due to a decrease in endothelial progenitor cells, primarily responsible for these repair processes. Regarding functional alterations, these consist of an imbalance

training program.

**2.1. Etiological factors**

*2.1.2. Environmental factors*

sympathetic hyperactivity [3–6].

*2.1.3. Possible pathological mechanisms*

*2.1.1. Genetics*

6].

**2. Pathological mechanisms**

Hypertension is the most prevalent cardiovascular disease (CVD), affecting 20–50% of the population in developed countries. Its prevalence increases with age, especially after 50 years old when it affects more than 50% of the population. All segments of the population (pregnant women, elderly, people with diabetes, etc.) are susceptible to developing a pathological elevation of blood pressure (BP). Hypertension is usually diagnosed when systolic blood pressure (SBP) is ≥140 mmHg and/or diastolic blood pressure (DBP) ≥90 mmHg, sustained constantly. However, the dividing line between normal blood pressure and hypertension is arbitrary and actually artificial. The value of BP is the result of the interaction of genetic and environmental factors (e.g., *polygenic inheritance, salt intake, smoking, stress, diet, etc.*).

A high BP has been identified as a risk factor for coronary artery disease (CAD), heart failure (HF), stroke, and peripheral arterial insufficiency. Hypertension is associated with earlier changes in organ systems, such as left ventricular (LV) hypertrophy, renal failure, retinopathy, and vascular dementia, which are grouped under the term "target organ damage" (TOD). Furthermore, hypertensive patients have a higher incidence of cardiovascular comorbidities (e.g., *diabetes, insulin resistance, dyslipidemia, etc.*) compared to the general population.

Currently, HBP represents a major challenge to public health as it is frequently associated with sudden death due to the silent nature of the condition. The first step is to secure a firm diagnosis. The European League of Hypertension recommends the use of an ambulatory BP measurement (monitoring ambulatory blood pressure (MAPA)), which is a device for automated blood pressure measurement repeatedly for 24 h. This monitoring test provides a more accurate picture of the circadian pattern of blood pressure changes over an average day and night. Recently, there has been a marked interest in this circadian pattern and the variability of BP because having an abnormal BP pattern has been related to increased cardiovascular risk and other health problems. In particular, night blood pressure seems to be the best predictor of cardiovascular events and the degree of development of cardiovascular disease. The MAPA can also differentiate permanent hypertension and hypertension secon‐ dary related to stress (white‐coat effect). Scientific evidence regarding the effectiveness of the MAPA has mainly emerged from the CARDIORISC project in Spain, which includes the largest global database available with more than 40,000 patients [2].

Inadequate treatment of hypertension increases drastically the potential damage on the main target organs (*e.g., heart, brain, kidney, retina, etc.*). There are several nonpharmacological strategies for preventing and treating hypertension, such as the DASH diet and physical activity. Recent evidence suggests that higher physical activity levels are associated not only with lower diurnal BP levels but also with lower levels of night BP, which represents a healthier circadian pattern and thus a reduced cardiovascular comorbidity. There is a considerable amount of scientific evidence, including meta‐analysis, supporting the antihypertensive effects of different types of exercise for blood pressure, such as continuous aerobic training. However, the appropriate type, intensity, time, and frequency of exercise remain unclear. In parallel, other types of exercise such as isometric strength training or high‐intensity aerobic training (HIT) are gaining attention in the literature, showing very promising results. In order to achieve and maximize the benefits of exercise safely, professionals should have updated guidelines for prescribing exercise for hypertension. These guidelines should be based on scientific evidence and provide precise practical information about how to design, implement, and control a training program.

#### **2. Pathological mechanisms**

#### **2.1. Etiological factors**

#### *2.1.1. Genetics*

increase will go from 972 million hypertensives in 2000 to 1,560,000,000 in 2025, representing

Hypertension is the most prevalent cardiovascular disease (CVD), affecting 20–50% of the population in developed countries. Its prevalence increases with age, especially after 50 years old when it affects more than 50% of the population. All segments of the population (pregnant women, elderly, people with diabetes, etc.) are susceptible to developing a pathological elevation of blood pressure (BP). Hypertension is usually diagnosed when systolic blood pressure (SBP) is ≥140 mmHg and/or diastolic blood pressure (DBP) ≥90 mmHg, sustained constantly. However, the dividing line between normal blood pressure and hypertension is arbitrary and actually artificial. The value of BP is the result of the interaction of genetic and

environmental factors (e.g., *polygenic inheritance, salt intake, smoking, stress, diet, etc.*).

(e.g., *diabetes, insulin resistance, dyslipidemia, etc.*) compared to the general population.

global database available with more than 40,000 patients [2].

A high BP has been identified as a risk factor for coronary artery disease (CAD), heart failure (HF), stroke, and peripheral arterial insufficiency. Hypertension is associated with earlier changes in organ systems, such as left ventricular (LV) hypertrophy, renal failure, retinopathy, and vascular dementia, which are grouped under the term "target organ damage" (TOD). Furthermore, hypertensive patients have a higher incidence of cardiovascular comorbidities

Currently, HBP represents a major challenge to public health as it is frequently associated with sudden death due to the silent nature of the condition. The first step is to secure a firm diagnosis. The European League of Hypertension recommends the use of an ambulatory BP measurement (monitoring ambulatory blood pressure (MAPA)), which is a device for automated blood pressure measurement repeatedly for 24 h. This monitoring test provides a more accurate picture of the circadian pattern of blood pressure changes over an average day and night. Recently, there has been a marked interest in this circadian pattern and the variability of BP because having an abnormal BP pattern has been related to increased cardiovascular risk and other health problems. In particular, night blood pressure seems to be the best predictor of cardiovascular events and the degree of development of cardiovascular disease. The MAPA can also differentiate permanent hypertension and hypertension secon‐ dary related to stress (white‐coat effect). Scientific evidence regarding the effectiveness of the MAPA has mainly emerged from the CARDIORISC project in Spain, which includes the largest

Inadequate treatment of hypertension increases drastically the potential damage on the main target organs (*e.g., heart, brain, kidney, retina, etc.*). There are several nonpharmacological strategies for preventing and treating hypertension, such as the DASH diet and physical activity. Recent evidence suggests that higher physical activity levels are associated not only with lower diurnal BP levels but also with lower levels of night BP, which represents a healthier circadian pattern and thus a reduced cardiovascular comorbidity. There is a considerable amount of scientific evidence, including meta‐analysis, supporting the antihypertensive effects of different types of exercise for blood pressure, such as continuous aerobic training. However, the appropriate type, intensity, time, and frequency of exercise remain unclear. In parallel, other types of exercise such as isometric strength training or high‐intensity aerobic training (HIT) are gaining attention in the literature, showing very promising results. In order to achieve

a raise of approximately 60% [1].

92 Fitness Medicine

From a clinical standpoint, the influence of genetics in hypertension is determined by a familial aggregation, so that the prevalence increases among relatives of first degree. Besides this clinical observation, knowledge of the genes involved in the development of hypertension is scarce. It seems clear that genetic determinants can be modified by environmental ones, so that the blood pressure or the resulting phenotype depends on the interaction of both factors. Genotypic and phenotypic research will be of great importance in the future as it may be able to help develop personalized treatments and prevention programs based on these findings [3– 6].

#### *2.1.2. Environmental factors*

The main factors related to the development of hypertension are linked to the progress and changes in lifestyle and diet. The mechanisms by which these environmental determinants increase blood pressure and promote the development of cardiovascular disease are not fully clarified but it seems that a high caloric intake and decreased energy expenditure produce sympathetic hyperactivity [3–6].

#### *2.1.3. Possible pathological mechanisms*

*1. Sympathetic overactivity*. It is characterized by an imbalance between sympathetic and parasympathetic activity. Sympathetic activation may be caused by a direct stimulus by chronic stress, high caloric intake, obesity, and physical inactivity among others. 2. *Renin-angiotensin system (RAS)*. The renin‐angiotensin system is undoubtedly mainly responsible for the development of vascular disease and one of the main focuses of therapeutic care. Angiotensin II is the main effector system with specific receptors at different levels that promote vasocon‐ striction and fluid retention, the latter thanks to the stimulation of adrenal aldosterone secretion as well as inflammatory, proaggregatory, and prothrombotic reactions. 3. *Dysfunction and endothelial injury*. The endothelium plays a fundamental role in vascular pathophysiology alterations observed in hypertension. Cardiovascular complications include both dysfunction and damage in the endothelial cell layer. In the latter case, the most plausible hypothesis is the inability of predisposed individuals to repair endothelial cell damage that occurs in normal circumstances, mainly due to a decrease in endothelial progenitor cells, primarily responsible for these repair processes. Regarding functional alterations, these consist of an imbalance between the production of vasodilator and anti-inflammatory substances including nitric oxide and the production of pro-inflammatory and primarily endothelin vasoconstrictors. 4. *Structural changes in the arteries*. Three types of changes in arteries are described in hypertension: the presence of capillary rarefaction, hypertrophy of the middle layer of resistance arteries, and stiffness of large arteries [3–6].

The evaluation of **vascular injury** is more complex and its relationship with prognosis is less evident. In particular, in regard to the modifications induced in the treatment, there is no universal recommendation for vascular assessment in hypertensive patients although there is evidence about the usefulness of the ankle arm index. The ankle arm index is an indicator of the existence of peripheral arterial disease and can be altered in apparently asymptomatic

Exercise for Hypertension http://dx.doi.org/10.5772/65035 95

The aim of an antihypertensive therapy is twofold. On one hand, reducing mortality and cardiovascular morbidity associated with increased pressure and, on the other, avoiding the progression and regression of subclinical visceral organ damage. Treatment should be initiated immediately in all patients with hypertension grade III (SBP of >180; DBP of >110), regardless of the presence of other conditions, and for any other hypertensive patients in the presence of diabetes, target organ damage, or chronic kidney disease established by cardiovascular disease. Although there is no clear consensus in the clinical guidelines, there is a general indication for starting treatment in elderly individuals at values above 150 mmHg 90 [3–6].

Diuretics are first-line drugs, and there is more evidence available of its protective capacity than with other drugs. There are three different subgroups of diuretics: thiazide, loop diuretics of Henle, and potassium-sparing, although only the former has clearly demonstrated a clear

There are three main groups of calcium-channel blockers. Their mechanism of action consists of the inhibition of dependent calcium channels in the membrane potential blocking the entry of calcium into the cell. The biggest drawback of these drugs is the frequent occurrence of side effects. In nearly a third of these patients, side effects are derived from cutaneous vasodilation and are primarily manifested by ankle edema. Calcium antagonists constitute one of the best options for a combined therapy. They have beneficial and synergistic effects when combined with RAS blockers (angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs)) and in the case of dihydropyridines, with beta blockers. In both cases, an additional antihypertensive benefit is achieved. Furthermore, the metabolic side effects of

The mechanism of action consists of the inhibition of angiotensin II formation from angiotensin I. ACEIs also cause a decrease in aldosterone secretion induced by angiotensin II and inhibit the breakdown of bradykinin to increase levels of the mentioned vasodilator peptide. They are currently considered a first step for drug treatment in hypertension, and have demonstrated

patients.

**5.1. Diuretics**

**5.2. Calcium antagonists**

diuretics are avoided.

**5. Drugs and pharmacology associated**

benefit in cardiovascular pressure in hypertensive patients.

**5.3. Inhibitors of the converting enzyme of angiotensin**

#### **3. Blood pressure monitoring (***random vs MAPA***)**

The diagnosis of hypertension and the therapeutic decisions derived from this diagnosis require the highest reliability possible. The difficulties in measuring the blood pressure of a subject are derived from its variability, associated mainly with his/her physical and mental activity, limitations in the accuracy of an indirect measure (with the observer as a major source of inaccuracy), and sometimes the alert reaction produced in a person to blood pressure monitoring, which in some cases can be of clinical relevance (white-coat phenomenon).

Measuring blood pressure in a clinical setting: the reference technique of measuring blood pressure has been classically performed in the clinical setting by the auscultatory technique with the mercury sphygmomanometer, and most recently by semiautomatic and validated self-measurement devices. Monitoring ambulatory blood pressure provides real value of great importance. MAPA keeps 24-h Holter records of the blood pressure of a person. The patient may be classified with respect to the values of blood pressure in four exclusive conditions: real normotensive, sustained hypertension, white-coat hypertension, and masked hypertension. Because of its advantages, MAPA is increasingly considered a necessary element in the basic assessment of hypertensive patients, with the recommendation of some clinical guidelines to use it for confirmation of diagnosis, previous to making therapeutic decisions [3–6].

#### **4. Morbidity of hypertension**

The main clinical guidelines for the diagnosis and treatment of hypertension advise for the evaluation, to the possible extent, of the existence of subclinical organ damage. The reason for this is the consideration of organ damage as an intermediate stage in the development of cardiovascular disease, with importance in the stratification of absolute cardiovascular risk, and therefore the need for a different therapeutic approach. Multiple components of subclinical organ damage in heart, renal, and cerebral level have been described [3–6].

#### **4.1. Main consequences**

In the **heart**, hypertension causes left ventricular hypertrophy, which is the first step for developing hypertensive heart disease.

The silent damage produced in the **kidney** should be assessed in all hypertensive patients at diagnosis. Furthermore, at least annually, the evaluation should proceed by determining serum creatinine, renal blood flow, as well as the microalbuminuria.

The evaluation of **vascular injury** is more complex and its relationship with prognosis is less evident. In particular, in regard to the modifications induced in the treatment, there is no universal recommendation for vascular assessment in hypertensive patients although there is evidence about the usefulness of the ankle arm index. The ankle arm index is an indicator of the existence of peripheral arterial disease and can be altered in apparently asymptomatic patients.

#### **5. Drugs and pharmacology associated**

The aim of an antihypertensive therapy is twofold. On one hand, reducing mortality and cardiovascular morbidity associated with increased pressure and, on the other, avoiding the progression and regression of subclinical visceral organ damage. Treatment should be initiated immediately in all patients with hypertension grade III (SBP of >180; DBP of >110), regardless of the presence of other conditions, and for any other hypertensive patients in the presence of diabetes, target organ damage, or chronic kidney disease established by cardiovascular disease. Although there is no clear consensus in the clinical guidelines, there is a general indication for starting treatment in elderly individuals at values above 150 mmHg 90 [3–6].

#### **5.1. Diuretics**

between the production of vasodilator and anti-inflammatory substances including nitric oxide and the production of pro-inflammatory and primarily endothelin vasoconstrictors. 4. *Structural changes in the arteries*. Three types of changes in arteries are described in hypertension: the presence of capillary rarefaction, hypertrophy of the middle layer of resistance

The diagnosis of hypertension and the therapeutic decisions derived from this diagnosis require the highest reliability possible. The difficulties in measuring the blood pressure of a subject are derived from its variability, associated mainly with his/her physical and mental activity, limitations in the accuracy of an indirect measure (with the observer as a major source of inaccuracy), and sometimes the alert reaction produced in a person to blood pressure monitoring, which in some cases can be of clinical relevance (white-coat phenomenon).

Measuring blood pressure in a clinical setting: the reference technique of measuring blood pressure has been classically performed in the clinical setting by the auscultatory technique with the mercury sphygmomanometer, and most recently by semiautomatic and validated self-measurement devices. Monitoring ambulatory blood pressure provides real value of great importance. MAPA keeps 24-h Holter records of the blood pressure of a person. The patient may be classified with respect to the values of blood pressure in four exclusive conditions: real normotensive, sustained hypertension, white-coat hypertension, and masked hypertension. Because of its advantages, MAPA is increasingly considered a necessary element in the basic assessment of hypertensive patients, with the recommendation of some clinical guidelines to

use it for confirmation of diagnosis, previous to making therapeutic decisions [3–6].

organ damage in heart, renal, and cerebral level have been described [3–6].

creatinine, renal blood flow, as well as the microalbuminuria.

The main clinical guidelines for the diagnosis and treatment of hypertension advise for the evaluation, to the possible extent, of the existence of subclinical organ damage. The reason for this is the consideration of organ damage as an intermediate stage in the development of cardiovascular disease, with importance in the stratification of absolute cardiovascular risk, and therefore the need for a different therapeutic approach. Multiple components of subclinical

In the **heart**, hypertension causes left ventricular hypertrophy, which is the first step for

The silent damage produced in the **kidney** should be assessed in all hypertensive patients at diagnosis. Furthermore, at least annually, the evaluation should proceed by determining serum

arteries, and stiffness of large arteries [3–6].

94 Fitness Medicine

**4. Morbidity of hypertension**

developing hypertensive heart disease.

**4.1. Main consequences**

**3. Blood pressure monitoring (***random vs MAPA***)**

Diuretics are first-line drugs, and there is more evidence available of its protective capacity than with other drugs. There are three different subgroups of diuretics: thiazide, loop diuretics of Henle, and potassium-sparing, although only the former has clearly demonstrated a clear benefit in cardiovascular pressure in hypertensive patients.

#### **5.2. Calcium antagonists**

There are three main groups of calcium-channel blockers. Their mechanism of action consists of the inhibition of dependent calcium channels in the membrane potential blocking the entry of calcium into the cell. The biggest drawback of these drugs is the frequent occurrence of side effects. In nearly a third of these patients, side effects are derived from cutaneous vasodilation and are primarily manifested by ankle edema. Calcium antagonists constitute one of the best options for a combined therapy. They have beneficial and synergistic effects when combined with RAS blockers (angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs)) and in the case of dihydropyridines, with beta blockers. In both cases, an additional antihypertensive benefit is achieved. Furthermore, the metabolic side effects of diuretics are avoided.

#### **5.3. Inhibitors of the converting enzyme of angiotensin**

The mechanism of action consists of the inhibition of angiotensin II formation from angiotensin I. ACEIs also cause a decrease in aldosterone secretion induced by angiotensin II and inhibit the breakdown of bradykinin to increase levels of the mentioned vasodilator peptide. They are currently considered a first step for drug treatment in hypertension, and have demonstrated their ability to prevent cardiovascular events in hypertensive patients. Combined therapies with thiazide and loop diuretics are especially effective as they prevent the formation of angiotensin II‐induced activation of renin secretion. One of its biggest advantages is that they are effective and safe in associated diseases, prolong survival, and reduce complications of patients with infarction and ventricular dysfunction. Likewise, these are required drugs in the treatment of heart failure and chronic renal failure with proteinuria. Finally, they are especially indicated in hypertension associated to diabetes mellitus due to its ability to prevent micro‐ and macrovascular coronary disease and nephropathy progression of secondary complica‐ tions. Side effects are mainly the appearance in some patients of refractory therapeutically nonproductive dry cough. There have also been reported isolated cases of angioedema, which appears with the first doses, probably reflecting a phenomenon of hypersensitivity.

**6.3. Ischemic heart disease**

with ischemic heart disease.

**6.4. Cerebrovascular disease**

**6.5. Kidney disease**

**6.6. Resistant hypertension**

**7. Exercise for hypertension**

onists have a special preventive capacity.

The objective of the control in these cases is to achieve figures lower than 140/90. Regardless of age, beta‐blockers are the drugs of choice in patients with hypertension and angina. Calcium antagonists are an alternative in case of contraindication or intolerance to beta‐blockers. It has also been found that spironolactone associated with beta‐blockers reduces mortality in heart failure. There are studies supporting the indication of ACE inhibitors or ARBs in all patients

Exercise for Hypertension http://dx.doi.org/10.5772/65035 97

Primary prevention constitutes one of the main expressions of the effectiveness of antihyper‐ tensive treatment control. Objectives are set here at values below 140/90 mmHg. Stroke especially affects the elderly hypertensive and depends markedly on the figures of control of the blood pressure. In clinical studies, it has been observed that diuretics and calcium antag‐

Hypertensive patients with albuminuria kidney disease or reduction of renal filtrate below 30

It is defined as the inability to achieve the desirable blood pressure despite modifications in lifestyle, the use of a diuretic, and at least two other blood pressure medicines. The prevalence is between 10 and 15%. Diagnosis requires confirmation by ambulatory monitoring (MAPA), since even a third of these patients present a white‐coat phenomenon. Many patients will need the administration of a fourth type of drug. A small group of patients maintains a high blood pressure despite complex therapeutic regimens often with up to six or seven drugs and by ruling out other causes responsible for resistance to treatment. Recently, some nonpharmaco‐ logical therapeutic techniques have been developed that have been proved effective in reducing blood pressure in these uncontrolled patients, such as renal sympathetic denervation,

Guidelines for the management of hypertension recommend lifestyle modifications, in particular, a combination of diet and exercise. Nonpharmacological strategies are aimed to change the lifestyle and should be instituted in hypertensive and pre‐hypertensive patients. Supervised exercise, the DASH diet, and weight reduction, combined with pharmacological therapy, are effective treatments for normalization of blood pressure. This statement is based on the knowledge that exercise is a landmark in primary prevention and coadjuvant in the treatment of hypertension [7]. Exercise is considered as a polypill and, thus, is necessary to

stimulation of carotid baroreceptors, or implantation of an arteriovenous fistula.

ml/min should be considered at high risk for injury in the target organ.

#### **5.4. Antagonists angiotensin II receptor**

These drugs reduce the inhibition of the renin‐angiotensin system by the specific antagonism of angiotensin I and II. The advantage compared to ACE inhibitors is that it is better tolerated. A unique feature is a major effect on stroke prevention.

#### **6. Hypertension in different biological conditions**

Treatment of hypertension in special situations deserves special consideration because of its high prevalence and its added cardiovascular risk [3–6]:

#### **6.1. Elderly**

In hypertensive patients over 80 years, treatment should start from equal or higher levels of 160/90 and with the goal of achieving values of 150/90. From this recommendation are excluded hypertensive patients with great fragility, high levels of dependence, or debilitating diseases in which treatment decisions should be individualized.

#### **6.2. Diabetes mellitus**

It is a situation of high cardiovascular risk. In addition, diabetic nephropathy is a serious health problem that can be the leading cause for a need of dialysis and kidney transplant. Prognosis of diabetic patients depends on many factors besides glycemic control, among which figures blood pressure. The basic objectives in this case are the reduction of blood pressure to levels below 140/90, and strict metabolic control of the glycosylated hemoglobin to levels lower than 7%, in addition to low‐density lipoprotein (LDL) cholesterol levels below 100 mg. The drug treatment for diabetic patients should be based on a serotonin‐releasing agent (SRA) blocking agent, especially because of its renal protective effect, although with most patients it will be necessary to use two or more associated drugs. In this case, the groups to combine would be calcium‐channel blockers and diuretics.

#### **6.3. Ischemic heart disease**

their ability to prevent cardiovascular events in hypertensive patients. Combined therapies with thiazide and loop diuretics are especially effective as they prevent the formation of angiotensin II‐induced activation of renin secretion. One of its biggest advantages is that they are effective and safe in associated diseases, prolong survival, and reduce complications of patients with infarction and ventricular dysfunction. Likewise, these are required drugs in the treatment of heart failure and chronic renal failure with proteinuria. Finally, they are especially indicated in hypertension associated to diabetes mellitus due to its ability to prevent micro‐ and macrovascular coronary disease and nephropathy progression of secondary complica‐ tions. Side effects are mainly the appearance in some patients of refractory therapeutically nonproductive dry cough. There have also been reported isolated cases of angioedema, which

appears with the first doses, probably reflecting a phenomenon of hypersensitivity.

These drugs reduce the inhibition of the renin‐angiotensin system by the specific antagonism of angiotensin I and II. The advantage compared to ACE inhibitors is that it is better tolerated.

Treatment of hypertension in special situations deserves special consideration because of its

In hypertensive patients over 80 years, treatment should start from equal or higher levels of 160/90 and with the goal of achieving values of 150/90. From this recommendation are excluded hypertensive patients with great fragility, high levels of dependence, or debilitating diseases

It is a situation of high cardiovascular risk. In addition, diabetic nephropathy is a serious health problem that can be the leading cause for a need of dialysis and kidney transplant. Prognosis of diabetic patients depends on many factors besides glycemic control, among which figures blood pressure. The basic objectives in this case are the reduction of blood pressure to levels below 140/90, and strict metabolic control of the glycosylated hemoglobin to levels lower than 7%, in addition to low‐density lipoprotein (LDL) cholesterol levels below 100 mg. The drug treatment for diabetic patients should be based on a serotonin‐releasing agent (SRA) blocking agent, especially because of its renal protective effect, although with most patients it will be necessary to use two or more associated drugs. In this case, the groups to combine would be

**5.4. Antagonists angiotensin II receptor**

**6.1. Elderly**

96 Fitness Medicine

**6.2. Diabetes mellitus**

calcium‐channel blockers and diuretics.

A unique feature is a major effect on stroke prevention.

high prevalence and its added cardiovascular risk [3–6]:

in which treatment decisions should be individualized.

**6. Hypertension in different biological conditions**

The objective of the control in these cases is to achieve figures lower than 140/90. Regardless of age, beta‐blockers are the drugs of choice in patients with hypertension and angina. Calcium antagonists are an alternative in case of contraindication or intolerance to beta‐blockers. It has also been found that spironolactone associated with beta‐blockers reduces mortality in heart failure. There are studies supporting the indication of ACE inhibitors or ARBs in all patients with ischemic heart disease.

#### **6.4. Cerebrovascular disease**

Primary prevention constitutes one of the main expressions of the effectiveness of antihyper‐ tensive treatment control. Objectives are set here at values below 140/90 mmHg. Stroke especially affects the elderly hypertensive and depends markedly on the figures of control of the blood pressure. In clinical studies, it has been observed that diuretics and calcium antag‐ onists have a special preventive capacity.

#### **6.5. Kidney disease**

Hypertensive patients with albuminuria kidney disease or reduction of renal filtrate below 30 ml/min should be considered at high risk for injury in the target organ.

#### **6.6. Resistant hypertension**

It is defined as the inability to achieve the desirable blood pressure despite modifications in lifestyle, the use of a diuretic, and at least two other blood pressure medicines. The prevalence is between 10 and 15%. Diagnosis requires confirmation by ambulatory monitoring (MAPA), since even a third of these patients present a white‐coat phenomenon. Many patients will need the administration of a fourth type of drug. A small group of patients maintains a high blood pressure despite complex therapeutic regimens often with up to six or seven drugs and by ruling out other causes responsible for resistance to treatment. Recently, some nonpharmaco‐ logical therapeutic techniques have been developed that have been proved effective in reducing blood pressure in these uncontrolled patients, such as renal sympathetic denervation, stimulation of carotid baroreceptors, or implantation of an arteriovenous fistula.

#### **7. Exercise for hypertension**

Guidelines for the management of hypertension recommend lifestyle modifications, in particular, a combination of diet and exercise. Nonpharmacological strategies are aimed to change the lifestyle and should be instituted in hypertensive and pre‐hypertensive patients. Supervised exercise, the DASH diet, and weight reduction, combined with pharmacological therapy, are effective treatments for normalization of blood pressure. This statement is based on the knowledge that exercise is a landmark in primary prevention and coadjuvant in the treatment of hypertension [7]. Exercise is considered as a polypill and, thus, is necessary to know the optimal dosage (posology) in order to obtain maximal benefits [8]. Specifically, the response of blood pressure to exercise aims to ensure adequate blood flow to active muscles. BP depends on cardiac output (Q), which varies depending on myocardial contractility, heart rate (HR), blood volume, and peripheral vascular resistance. During the development of training, changes occur at the cardiovascular level, including increased systolic blood pressure, diastolic blood pressure, and mean arterial pressure (MAP) [9, 10].

in 5–7 mmHg [17]. However, it should also be noted that there is a considerable heterogeneity of the individual response to exercise training, attributed to environmental and genetic factors.

Exercise for Hypertension http://dx.doi.org/10.5772/65035 99

PEH is mediated by both central and peripheral factors. The fall in blood pressure seen after exercise seems to be caused by a reduced signal transduction from sympathetic nerve activa‐ tion into vasoconstriction, and also local vasodilatator mechanisms. Recent evidence suggests

Chronic aerobic exercise in hypertensive patients may lead to a reduction in left ventricular mass [16], although results are not always conclusive. Decreased oxidative stress and inflam‐ mation levels, as well as an improved autonomic function, have been described as key mechanisms that contribute to the physiological benefits obtained with exercise. However, further research is needed to elucidate the exact mechanisms involved in the adaptations to

When it comes to prescribe physical activity, the dose‐response question is a very relevant issue. It refers to the relationship between different doses of physical activity and changes in a defined health parameter. The total physiological load is calculated for continuous endurance training as the product of the intensity, duration, and frequency of the exercise. There is still an ongoing debate about the optimal training dose, frequency, duration, and intensity of

In regard to intensity, few studies have actually compared the effects of different intensities of endurance exercise in blood pressure. Cornelissen et al. [20], using a randomized crossover design, compared the effects of two different programs of endurance training in BP, HR, and heart rate variability (HRV) in a group of 36 healthy sedentary older adults (mean age: 59 years, range: 55–71 years) with SBP of ≥120 mmHg or DBP of ≥80 mmHg. The study was composed of three 10‐week periods. In the first and third period, the participants exercised at 33 or 66% of HR reserve (3 days per week, 50 min per session) in random order, with a sedentary period in between. The results of this study showed that endurance training at both lower and higher intensities reduced SBP significantly (*P* < 0.05) at rest, before exercise, during exercise, and during recovery to a similar extent. The effect of training on HR was more pronounced (*P* <

However, more recent evidence suggests that moderate to high intensities produce higher BP reductions than low‐intensity endurance training (<40% of heart rate reserve or <55% of

On the other hand, the most appropriate duration and frequency of the exercise programs is not fully clear either, but most evidence is in line with the American College on Sports Medicine's recommendations of performing aerobic exercise most, preferably all, days of the

0.05) with higher intensity, whereas HRV was unaffected by the intervention.

week. The duration of each exercise session should range from 30 to 60 min [11].

About 20–25% of hypertensive patients could be nonrespondents to exercise [18].

that muscle afferents may play a major role in this response [19].

*<IP_ADDRESS>. Mechanisms of benefits*

chronic aerobic exercise [16].

exercise for hypertensive patients.

maximum heart rate) [17].

*<IP_ADDRESS>. Dose of exercise*

The possible mechanisms of the antihypertensive effects of exercise are not fully clear but may include [7] (a) reduction in sympathetical‐induced vasoconstriction and reduced catechola‐ mine segregation; (b) increased insulin sensitivity; (c) anti‐inflammatory effects; and (d) vascular structural adaptations.

Different international organizations such as the American Heart Association, American College of Cardiology, American College of Sports Medicine, European Society of Hyperten‐ sion, European Society of Cardiology, or the Canadian Hypertension Education Program have developed their exercise prescription guidelines for adults with hypertension (for a review, see the original statements or Pescatello et al. [11]). Because the ideal dose is still unknown, the emergence of new modalities of exercise, in this chapter updated exercise strategies for managing and preventing hypertension, is presented. The modalities of exercise that have shown a relatively stronger supporting evidence are aerobic exercise (Class I, level of evidence A), dynamic resistance exercise (Class IIA, level of evidence B), and isometric handgrip (Class IIB, level of evidence C) [3].

#### **7.1. Cardiovascular exercise**

Low aerobic fitness has been proved to be a strong predictor for future cardiovascular disease and all‐cause mortality in people with hypertension [12]. Not surprisingly therefore, there still seems to be a consensus that aerobic exercise should be prescribed as the primary type of exercise for the prevention, treatment, and control of hypertension [11]. Aerobic training can be performed either at continuous intensity or by short intervals of high‐intensity exercise.

#### *7.1.1. Continuous aerobic*

The most extensive evidence with endurance training for hypertension is available for the continuous modality, understood as exercise of a constant sustainable intensity that is carried out over a given period of time, usually long.

#### *<IP_ADDRESS>. Benefits of continuous aerobic training for hypertension*

An acute session of continuous aerobic exercise can lower BP during the post‐exercise period, known as the post‐exercise hypotension (PEH). PEH is considered a prolonged decrease in resting blood pressure in the minutes and hours (up to 24 h) after an acute bout of exercise [13]. This decrease is more pronounced in hypertensive patients [14] and has also been shown in very old adults [15].

Chronic exercise results in more sustained reductions in BP, known as the exercise‐training response [16]. According to different reviews and meta‐analysis, aerobic exercise reduces BP in 5–7 mmHg [17]. However, it should also be noted that there is a considerable heterogeneity of the individual response to exercise training, attributed to environmental and genetic factors. About 20–25% of hypertensive patients could be nonrespondents to exercise [18].

#### *<IP_ADDRESS>. Mechanisms of benefits*

know the optimal dosage (posology) in order to obtain maximal benefits [8]. Specifically, the response of blood pressure to exercise aims to ensure adequate blood flow to active muscles. BP depends on cardiac output (Q), which varies depending on myocardial contractility, heart rate (HR), blood volume, and peripheral vascular resistance. During the development of training, changes occur at the cardiovascular level, including increased systolic blood pressure,

The possible mechanisms of the antihypertensive effects of exercise are not fully clear but may include [7] (a) reduction in sympathetical‐induced vasoconstriction and reduced catechola‐ mine segregation; (b) increased insulin sensitivity; (c) anti‐inflammatory effects; and (d)

Different international organizations such as the American Heart Association, American College of Cardiology, American College of Sports Medicine, European Society of Hyperten‐ sion, European Society of Cardiology, or the Canadian Hypertension Education Program have developed their exercise prescription guidelines for adults with hypertension (for a review, see the original statements or Pescatello et al. [11]). Because the ideal dose is still unknown, the emergence of new modalities of exercise, in this chapter updated exercise strategies for managing and preventing hypertension, is presented. The modalities of exercise that have shown a relatively stronger supporting evidence are aerobic exercise (Class I, level of evidence A), dynamic resistance exercise (Class IIA, level of evidence B), and isometric handgrip (Class

Low aerobic fitness has been proved to be a strong predictor for future cardiovascular disease and all‐cause mortality in people with hypertension [12]. Not surprisingly therefore, there still seems to be a consensus that aerobic exercise should be prescribed as the primary type of exercise for the prevention, treatment, and control of hypertension [11]. Aerobic training can be performed either at continuous intensity or by short intervals of high‐intensity exercise.

The most extensive evidence with endurance training for hypertension is available for the continuous modality, understood as exercise of a constant sustainable intensity that is carried

An acute session of continuous aerobic exercise can lower BP during the post‐exercise period, known as the post‐exercise hypotension (PEH). PEH is considered a prolonged decrease in resting blood pressure in the minutes and hours (up to 24 h) after an acute bout of exercise [13]. This decrease is more pronounced in hypertensive patients [14] and has also been shown in

Chronic exercise results in more sustained reductions in BP, known as the exercise‐training response [16]. According to different reviews and meta‐analysis, aerobic exercise reduces BP

diastolic blood pressure, and mean arterial pressure (MAP) [9, 10].

vascular structural adaptations.

98 Fitness Medicine

IIB, level of evidence C) [3].

**7.1. Cardiovascular exercise**

*7.1.1. Continuous aerobic*

very old adults [15].

out over a given period of time, usually long.

*<IP_ADDRESS>. Benefits of continuous aerobic training for hypertension*

PEH is mediated by both central and peripheral factors. The fall in blood pressure seen after exercise seems to be caused by a reduced signal transduction from sympathetic nerve activa‐ tion into vasoconstriction, and also local vasodilatator mechanisms. Recent evidence suggests that muscle afferents may play a major role in this response [19].

Chronic aerobic exercise in hypertensive patients may lead to a reduction in left ventricular mass [16], although results are not always conclusive. Decreased oxidative stress and inflam‐ mation levels, as well as an improved autonomic function, have been described as key mechanisms that contribute to the physiological benefits obtained with exercise. However, further research is needed to elucidate the exact mechanisms involved in the adaptations to chronic aerobic exercise [16].

#### *<IP_ADDRESS>. Dose of exercise*

When it comes to prescribe physical activity, the dose‐response question is a very relevant issue. It refers to the relationship between different doses of physical activity and changes in a defined health parameter. The total physiological load is calculated for continuous endurance training as the product of the intensity, duration, and frequency of the exercise. There is still an ongoing debate about the optimal training dose, frequency, duration, and intensity of exercise for hypertensive patients.

In regard to intensity, few studies have actually compared the effects of different intensities of endurance exercise in blood pressure. Cornelissen et al. [20], using a randomized crossover design, compared the effects of two different programs of endurance training in BP, HR, and heart rate variability (HRV) in a group of 36 healthy sedentary older adults (mean age: 59 years, range: 55–71 years) with SBP of ≥120 mmHg or DBP of ≥80 mmHg. The study was composed of three 10‐week periods. In the first and third period, the participants exercised at 33 or 66% of HR reserve (3 days per week, 50 min per session) in random order, with a sedentary period in between. The results of this study showed that endurance training at both lower and higher intensities reduced SBP significantly (*P* < 0.05) at rest, before exercise, during exercise, and during recovery to a similar extent. The effect of training on HR was more pronounced (*P* < 0.05) with higher intensity, whereas HRV was unaffected by the intervention.

However, more recent evidence suggests that moderate to high intensities produce higher BP reductions than low‐intensity endurance training (<40% of heart rate reserve or <55% of maximum heart rate) [17].

On the other hand, the most appropriate duration and frequency of the exercise programs is not fully clear either, but most evidence is in line with the American College on Sports Medicine's recommendations of performing aerobic exercise most, preferably all, days of the week. The duration of each exercise session should range from 30 to 60 min [11].

In parallel, Cornelissen and Smart [17] concluded, after conducting a systematic review and meta‐analysis, that exercise programs longer than 210 min per week produced the smallest reductions in BP compared to shorter programs, but probably due to the lower intensity of longer programs.

In patients with coronary artery disease and heart failure, it has been suggested that short bouts of high‐intensity exercise (100% of maximal aerobic power) such as 15 s for people with CAD and 30 s for people with HF (with passive recovery phases of the same duration between bouts, ratio 1:1) are optimal for obtaining benefits and improving adherence [26]. It is possible that these combinations are also adequate for people with hypertension as shown by Sosner et al. [25], but more research is needed in order to establish the most appropriate training

Exercise for Hypertension http://dx.doi.org/10.5772/65035 101

Resistance exercise is increasingly recommended because studies have shown a reduced systolic blood pressure of 1.8 and 3.3 mmHg in diastolic blood pressure with this type of

Initially, SBP and DBP rise because of the exercise pressor reflex to the cardiovascular center in the medulla from proprioceptors (mechanoreceptors and metaboreceptors) in active muscles. Arterial pressure rises to overcome the resistance to muscle perfusion caused by

A hypotensive response has been reported several hours after exercise, caused by reduced norepinephrine levels and thus by the inhibition of sympathetic activity, a reduction in circulating angiotensin II, adenosine, and endothelin levels and their receptors in the central nervous system leading to decreased pulmonary vascular resistance (PVR), and increased baroreflex sensitivity. Hypotension is also triggered by the vasodilator effect of prostaglandins

As a general recommendation, Pescatello et al. [11] recommend to carry out a strength‐training program of moderate intensity (i.e., 60–80% of 1 RM) consisting of eight to 10 exercises targeting the major muscle groups (performing multisets of 10–12 reps), and using different means of resistance training. This training should ideally be repeated 2–3 days per week.

Usually, it has been recommended to perform strength training dynamically, perhaps to avoid an increase in blood pressure. This effect is possibly due to a mechanical compression, causing increased peripheral resistance. Such resistance is related to blood viscosity and the length and radius of the vessel during muscle contraction in exercised muscle groups. This compression phenomenon that obstructs blood flow is associated with a reflex vasoconstriction in unexer‐ cised body areas that elevate BP. Moreover, when holding the breath while performing strength training (usually when the load is very high), an increase in the intrathoracic pressure caused by what is known as the Valsalva maneuver (MV) occurs [27]. Fleck et al. [28] observed that the SBP, DBP, and the double product (DP) increase during the last repetitions (one to three)

regime.

training [17].

and nitric oxide.

*7.2.3. Dose of exercise*

*7.2.2. Mechanisms of benefits*

**7.2. Resistance exercise: dynamic resistance training**

*7.2.1. Benefits of dynamic resistance training for hypertension*

elevated intramuscular pressure interrupting arterial blood flow.

#### *7.1.2. High-intensity interval training*

There is increasing evidence showing that high‐intensity training (85–100% of peak oxygen uptake [VO2peak]) in hypertensive patients may elicit higher CVD benefits, including lowering blood pressure, compared to low‐ and moderate‐intensity training [20, 21]. High‐intensity interval training (HITT) is the most common form of high‐intensity training, and consists of short bouts of high‐intensity exercise interspersed with resting periods of similar, lower, or longer duration.

#### *<IP_ADDRESS>. Benefits of HIIT for hypertension*

Repeated bouts of high‐intensity interval exercise (>85 VO2max) have been shown to induce similar PEH responses to those obtained with continuous modalities of endurance training performed at lower intensities (∼60 to 65% VO2max), both when matched for exercise volume [22], and when compared to lower volume but performed at maximal intensity [23].

A 12‐week HIIT program (85–90% of VO2max) lowered blood pressure, improved cardiac function and aerobic capacity, and reduced the mean HR, with superior effects than continuous aerobic training performed at a lower intensity (60% of VO2max) [21].

#### *<IP_ADDRESS>. Mechanisms of benefits*

The mechanisms of the benefits elicited by HIIT programs are probably similar to the ones described in the continuous modality. However, higher intensities elicit exponentially greater increases in sympathetic activity, so it is possible that it may produce higher autonomic adaptations. It has also been suggested that the larger shear stress provided by high‐intensity exercise compared to moderate intensity programs further enhances the endothelial function, which plays a major role in the regulation of vasomotor tone and the development of athero‐ sclerosis, and it has also been shown to be a strong predictor of CV risk in hypertensive patients [21–25].

#### *<IP_ADDRESS>. Dose of exercisee*

When it comes to HIIT training, the most important variables to consider are the duration of the short bouts of high‐intensity exercise as well as the duration of the resting periods. More research is needed for establishing the optimal ratio of exercise and rest in people with hypertension, with protocols ranging from 4 × 4‐min interval at 85–90% of VO2max with a 3‐min active pause between bouts [21] to two sets of 10 min composed of repeated phases of 15 s at 100% interspersed by 15 s of passive recovery, with another 4 min of passive recovery between sets [25].

In patients with coronary artery disease and heart failure, it has been suggested that short bouts of high‐intensity exercise (100% of maximal aerobic power) such as 15 s for people with CAD and 30 s for people with HF (with passive recovery phases of the same duration between bouts, ratio 1:1) are optimal for obtaining benefits and improving adherence [26]. It is possible that these combinations are also adequate for people with hypertension as shown by Sosner et al. [25], but more research is needed in order to establish the most appropriate training regime.

#### **7.2. Resistance exercise: dynamic resistance training**

#### *7.2.1. Benefits of dynamic resistance training for hypertension*

Resistance exercise is increasingly recommended because studies have shown a reduced systolic blood pressure of 1.8 and 3.3 mmHg in diastolic blood pressure with this type of training [17].

#### *7.2.2. Mechanisms of benefits*

In parallel, Cornelissen and Smart [17] concluded, after conducting a systematic review and meta‐analysis, that exercise programs longer than 210 min per week produced the smallest reductions in BP compared to shorter programs, but probably due to the lower intensity of

There is increasing evidence showing that high‐intensity training (85–100% of peak oxygen uptake [VO2peak]) in hypertensive patients may elicit higher CVD benefits, including lowering blood pressure, compared to low‐ and moderate‐intensity training [20, 21]. High‐intensity interval training (HITT) is the most common form of high‐intensity training, and consists of short bouts of high‐intensity exercise interspersed with resting periods of similar, lower, or

Repeated bouts of high‐intensity interval exercise (>85 VO2max) have been shown to induce similar PEH responses to those obtained with continuous modalities of endurance training performed at lower intensities (∼60 to 65% VO2max), both when matched for exercise volume

A 12‐week HIIT program (85–90% of VO2max) lowered blood pressure, improved cardiac function and aerobic capacity, and reduced the mean HR, with superior effects than continuous

The mechanisms of the benefits elicited by HIIT programs are probably similar to the ones described in the continuous modality. However, higher intensities elicit exponentially greater increases in sympathetic activity, so it is possible that it may produce higher autonomic adaptations. It has also been suggested that the larger shear stress provided by high‐intensity exercise compared to moderate intensity programs further enhances the endothelial function, which plays a major role in the regulation of vasomotor tone and the development of athero‐ sclerosis, and it has also been shown to be a strong predictor of CV risk in hypertensive

When it comes to HIIT training, the most important variables to consider are the duration of the short bouts of high‐intensity exercise as well as the duration of the resting periods. More research is needed for establishing the optimal ratio of exercise and rest in people with hypertension, with protocols ranging from 4 × 4‐min interval at 85–90% of VO2max with a 3‐min active pause between bouts [21] to two sets of 10 min composed of repeated phases of 15 s at 100% interspersed by 15 s of passive recovery, with another 4 min of passive recovery between

[22], and when compared to lower volume but performed at maximal intensity [23].

aerobic training performed at a lower intensity (60% of VO2max) [21].

longer programs.

100 Fitness Medicine

longer duration.

*7.1.2. High-intensity interval training*

*<IP_ADDRESS>. Benefits of HIIT for hypertension*

*<IP_ADDRESS>. Mechanisms of benefits*

patients [21–25].

sets [25].

*<IP_ADDRESS>. Dose of exercisee*

Initially, SBP and DBP rise because of the exercise pressor reflex to the cardiovascular center in the medulla from proprioceptors (mechanoreceptors and metaboreceptors) in active muscles. Arterial pressure rises to overcome the resistance to muscle perfusion caused by elevated intramuscular pressure interrupting arterial blood flow.