hypertension is a multifactorial condition characterized by high and sustained levels of blood pressure ( bp ) .
it is the most common condition in primary care and often associated with functional and/or structural changes in target organs and metabolic disorders , increasing the risk of fatal and nonfatal cardiovascular events [ 1 , 2 ] . among the risk factors for mortality from cardiovascular disease ( cvd )
, hypertension explains 40% and 25% of deaths from stroke and coronary artery disease ( cad ) , respectively .
endothelial cells of the vascular system are responsible for many biochemical reactions that maintain vascular homeostasis and consequently the bp levels . endothelium modulates vascular tone , not only by producing vasodilator substances but also by releasing vasoconstrictive substances through prostanoid of endothelin generation , as well as through conversion of angiotensin i ( ai ) in angiotensin ii ( aii ) on the endothelial surface .
these vasoconstrictor agents not only act mainly locally but also present some systemic effects , playing an important role in regulating the vascular function and remodeling the arterial wall . in healthy individuals
, there is a balance among these substances , tending to vasodilatation when endothelial function is normal .
changes in endothelial function precede morphological changes of blood vessels and contribute to the development of clinical complications of cardiovascular diseases .
thus , the beginning and the clinical course of adverse cardiovascular events depend directly on changes in vascular biology .
the limited no bioavailability is the main mechanism involved in endothelial dysfunction , which is crucial for the development of cvd .
in fact , endothelial dysfunction in peripheral and coronary vessels is an independent predictor of cardiovascular events and represents an early stage of cad .
as endothelial dysfunction is reversible , early detection and intervention could have critical therapeutic and prognostic implications for patients with risk for , or even with established , cvd [ 7 , 8 ] .
therefore , an improvement in the no bioavailability can have a major effect on endothelial function and , consequently , on cvd prevention and treatment [ 9 , 10 ] .
metabolic syndrome can be considered a clinical and biochemical expression of insulin resistance , representing a clustering of central obesity , hypertension , hyperglycemia , and dyslipidemia [ 19 , 20 ] .
recently , experimental models and clinical studies demonstrated that reductions in the no bioavailability play a central role in the pathophysiology of metabolic dysfunction .
endothelial nitric oxide synthase- ( enos- ) deficient mice were able to develop high bp and metabolic dysfunction , and both might be the result of insulin resistance [ 21 , 22 ] . in the same experimental model ,
the amount of dietary nitrate used for this effect was comparable to those derived from enos under normal conditions , which corresponds to a rich intake of vegetables for humans . besides , dietary nitrate was able to increase tissue and plasma levels of bioactive nitrogen oxides .
lastly , chronic nitrate supplementation prevented the prediabetic phenotype in these animals by reducing visceral fat accumulation and circulating levels of triglycerides .
in humans , enos polymorphisms have been associated with insulin resistance , type 2 diabetes mellitus , and metabolic syndrome .
furthermore , recent evidences have shown that obese subjects present a reduced ability to produce no [ 10 , 24 ] .
therefore , the dietary nitrate has been widely studied in clinical trials as an alternative form of the classical pathway of l - arginine to no production .
poor eating habits may be considered as risk factors for cvd . in fact , high intake of foods rich in cholesterol , lipids , and saturated fatty acids and low consumption of fiber sources are related to dyslipidemia , obesity , diabetes mellitus , and hypertension .
thus , nutritional interventions associated with changes in lifestyle are recognized as important strategies for primary prevention of hypertension and are auxiliary to pharmacological therapies to reduce cardiovascular risk .
epidemiological evidences suggest that vegetable consumption reduces bp and risk of cvd [ 2729 ] .
dash ( dietary approach to stop hypertension ) eating plan is one of the major effective strategies for prevention and nonpharmacological management of hypertension .
this eating proposal highlights the importance of increasing fruit and vegetables intake , and recent research suggests that the beneficial effects of dash plan on bp are related to high inorganic nitrate content of food included in this eating plan ( e.g. , green leaves and root vegetables ) [ 32 , 33 ] .
beetroots , lettuce , chard , arugula , and spinach are the vegetables containing the highest amount of nitrate , > 250  mg  nitrate/100  g .  
beetroot is a vegetable , particularly rich in inorganic nitrate , which contains an average of 2056  mg of nitrate in a traditional cultivation .
there are some studies using beetroot to test the effects of inorganic nitrate intake on bp .
nitrate ( no3 ) and nitrite ( no2 ) , present in beetroot and in other food sources , were recently related to cardiovascular benefits .
however , they were previously considered as toxic compounds due to the development of malignancies such as gastric cancer . therefore , strict rules regarding these inorganic anions are regulated in food and in drinking water . beetroot and other vegetables sources of nitrate contain approximately 6080% of the daily nitrate intake in the western population .
nitrate content in vegetables may be influenced by factors related to the plant itself , such as variety , species , and maturity , and to the environment , such as temperature , light intensity , lack of some nutrients , and fertilizer use .
international organizations indicate that the consumption of dietary nitrate is about 31 to 185  mg / day in europe and 40 to 100  mg / day in usa , and the oral bioavailability of dietary nitrate is 100% . in 1962 , world health organization ( who ) set an upper limit of nitrate consumption in food .
an acceptable daily intake is 3.7  mg no3/body weight ( kg ) , which is the same value adopted by the european authority for food safety .
this amount is equivalent to 300  mg / day for an adult weighing 80  kg .
after intake , dietary nitrate quickly increases in plasma , in about 30 minutes , reaching its peak in 90 minutes .
in contrast , nitrite levels are considerably slower in circulation , reaching their peak in 2.5 to 3 hours .
most of inorganic nitrate , about 75% of absorbed nitrate , is excreted in urine and 25% of plasma nitrate is excreted in saliva [ 18 , 39 ] .
the exact mechanism of salivary concentration is unknown . as a result , there is supply of substrate for nitrate reductase expressed by bacteria that colonize the dorsal surface of the tongue , resulting in reduction of nitrate to nitrite .
after nitrite is then swallowed , the stomach and the acid environment reduce it to no .
no and nitrite continue through the systemic circulation , and the remaining nitrite is reduced to no in high resistance vessels , promoting vasodilatation and consequently lowering bp   ( figure 1 ) . both no3 and no2 from diet and via l - arginine participate in the no synthesis
lately , there is a growing body of interest on the role of these two anions in biological function .
the improvement in vascular dysfunction and in bp levels after dietary nitrate seems to be mediated by effects on oxidative stress and inflammation [ 42 , 43 ] .
after an acute intake of beetroot juice ( 500  ml ) , it is possible to observe reduction of 10  mmhg in systolic bp ( after 2.5  h ) and reduction of 8  mmhg in diastolic bp ( after 3  h ) in healthy individuals .
the decrease in bp was sustained after 24  h of juice intake . the highest reduction in bp
liu et al . evaluated the effects of a meal rich in nitrate ( based on spinach consumption ) on bp and arterial stiffness in healthy individuals .
two hours after a nitrate - rich meal consumption ( 220  mg nitrate ) , there was a larger artery elasticity index , lower pulse pressure , and lower systolic bp compared to the values after a standard meal , low in nitrate .
recent experimental studies [ 23 , 45 , 46 ] and clinical trials have shown that nitrate dietary intakes from beetroot juice [ 18 , 47 ] , beet - enriched bread , or inorganic nitrate supplements   have a protective effect against cvd because of reducing bp , platelet aggregation inhibition , and prevention of endothelial dysfunction . recently , bondonno et al . have shown that chronic ingestion of beetroot juice ( one week , 420  mg  nitrate / day ) did not improve the bp control in treated hypertensive patients . in another study with overweight elderly subjects , jajja et al
. showed reduction of 7  mmhg in systolic bp , after three weeks of beetroot juice intake ( 350  mg nitrate / day ) .
however , when bp was evaluated for 24 hours by ambulatory blood pressure monitoring ( abpm ) , no significant changes were shown in bp levels .  
table 2 shows some clinical trials that evaluated the effects of nitrate intake on bp and vascular function .
in fact , there is no consensus about the effects of dietary inorganic nitrates on bp and endothelial function , and their effects on cardiovascular health , despite studies with positive results . since the initial investigations in healthy volunteers , studies using inorganic nitrate and formulations with nitrate salt showed promising results reducing bp , with nitrate doses ranging from 155 to 1484  mg / day , between 1 and 15 days , with reductions of 4  mmhg in systolic bp and of 1  mmhg in diastolic bp [ 33 , 50 ] . in hypertensive patients , systolic bp
remained significantly reduced in approximately 8  mmhg over 24 hours after the intervention , which is similar to the reduction provided by drug therapy ( 9  mmhg ) .
this is important because the ingestion of dietary nitrate in a single dose per day may be sufficient to achieve benefits in lowering bp [ 50 , 51 ] .
increasing nitrite levels by nitrate intake appears to have beneficial effects in many physiologic and clinical settings .
several clinical trials are being conducted to determine the great therapeutic potential of increasing the bioavailability of nitrite in human health and disease , including studies related to vascular aging .
nevertheless , there are many limitations in nitrate studies , such as the type of population enrolled in each trial and the dependent effect of the baseline bp .
therefore , the effects are unlikely to be the same among healthy and hypertensive individuals . in addition , when evaluating treated hypertensive patients , use of medications , such as calcium channel antagonists , may affect endothelial function and hence can interfere in some vascular parameters .
sample size is also a limiting factor considering the fact that it is small in most of nitrate studies . indeed , large clinical trials are necessary to confirm the potential beneficial effects of inorganic nitrate in patients with cvd . even with these considerations ,
dietary nitrate seems to represent an inexpensive and a promising complementary therapy to support hypertension treatment with benefits for cardiovascular health .
 poor eating habits may represent cardiovascular risk factors since high intake of fat and saturated fatty acids contributes to dyslipidemia , obesity , diabetes mellitus , and hypertension . 
 thus , nutritional interventions are recognized as important strategies for primary prevention of hypertension and as adjuvants to pharmacological therapies to reduce cardiovascular risk . 
 the dash ( dietary approach to stop hypertension ) plan is one of the most effective strategies for the prevention and nonpharmacological management of hypertension . 
 the beneficial effects of dash diet on blood pressure might be related to the high inorganic nitrate content of some food products included in this meal plan . 
 the beetroot and other food plants considered as nitrate sources account for approximately 6080% of the daily nitrate exposure in the western population . 
 the increased levels of nitrite by nitrate intake seem to have beneficial effects in many of the physiological and clinical settings . 
 several clinical trials are being conducted to determine the broad therapeutic potential of increasing the bioavailability of nitrite in human health and disease , including studies related to vascular aging . in conclusion , the dietary inorganic nitrate seems to represent a promising complementary therapy to support hypertension treatment with benefits for cardiovascular health . 
1. Introduction
2. Nitric Oxide (NO), Endothelial Dysfunction, and Metabolic Syndrome
3. Sources and Beneficial Effects of Dietary Nitrate
4. Effects of Dietary Nitrate on Blood Pressure
5. Conclusion