Atenolol and bendrofluazide in hypertension. ACE inhibitors, beta-blockers, calcium blockers, and diuretics for the control of systolic hypertension. Partial regression of vascular structural alterations in hypertensive patients treated with alpha-beta-blocker, labetalol. Mindfulness-based stress reduction and physiological activity during acute stress: a randomized controlled trial. Antihypertensive efficacy and side effects of three beta‐blockers and a diuretic in elderly hypertensives: a report from the STOP‐Hypertension study Beta-blockers versus diuretics in hypertensive men: main results from the HAPPHY trial. Efficacy of candesartan cilexetil as add-on therapy in hypertensive patients uncontrolled on background therapy: a clinical experience trial. ACTION Study Investigators. [Renal hemodynamics and proteinuria in chronic glomerulonephritis treated with beta-receptor blockers or ace inhibitors]. Beta-blockers do not impair the cardiovascular benefits of endurance training in hypertensives Effects of landiolol, a short-acting beta-1 blocker, on hemodynamic variables during emergence from anesthesia and tracheal extubation in elderly patients with and without hypertension A 16-week, randomized, double-blind, placebo-controlled, crossover trial to quantify the combined effect of an angiotensin-converting enzyme inhibitor and a beta-blocker on blood pressure reduction. Nutritional dose of magnesium in hypertensive patients on beta blockers lowers systolic blood pressure: a double-blind, cross-over study. [Efficacy of monotherapy with 15 antihypertensive agents in treating essential hypertension assessed by 24-hour ambulatory blood pressure monitoring].
The effect of atenolol , a new beta-1-adrenergic receptor blocking agent , was studied in a double-blind cross-over trial in 24 carefully selected hypertensive out patients . After a four-week run-in period on matching placebo each patient received atenolol 200 mg/day , atenolol 400 mg/day , a combination of atenolol 200/mg day with bendrofluazide 5 mg/day , and bendrofluazide 5 mg/day alone , according to a r and om sequence . Atenolol at either dose produced a significantly greater reduction in all blood pressure levels except st and ing systolic pressure than bendrofluazide alone . There was no statistically significant difference between the effects of the two atenolol doses on either blood pressure or pulse rate . The addition of bendrofluazide to atenolol result ed in a further significant lowering of the blood pressure . A significant effect of thiazide on weight was noted . The study shows that atenolol , a cardioselective beta-blocker of similar potency to propranolol in animals but without membrane-stabilizing or partial agonist acitivity , is an effective and well-tolerated hypotensive agent The objective of this study was to determine which of the common groups of antihypertensive drugs is most effective at lowering systolic blood pressure ( SBP ) in elderly patients with previously untreated hypertension and the percentage of patients controlled with single or sequential monotherapy . Subjects were recruited from patients attending other outpatient clinics and entered into the study if their SBP was more than 150 mm Hg after three visits . Patients were given a low and high dose of each of the main classes of drugs or placebo for 1 month each . The study was a balanced , r and omized crossover design with five periods : placebo ; angiotensin converting enzyme inhibitors ; beta-blocking drugs ; calcium-blocking drugs ; and thiazide diuretics .  Blood pressure ( BP ) was measured 24 to 26 h after the previous dose . A question naire for side effects was administered at each visit . Seventy-four patients entered the study . beta-Blockers could not be used in 15 patients because of asthma or bronchospasm and these had two placebo periods . There were 9 of 66 patients on P , 9 of 46 on beta-blockers , 4 of 65 on calcium-blocking drugs , 4 of 65 on diuretic , and 1 of 62 patients on ACE inhibitors who did not progress to the higher dose because of side effects . Decreases in SBP compared to r and omized placebo were calcium-blocking drugs 15 mm Hg = diuretic 13 mm Hg > ACE inhibitors 8 mm Hg = beta-blockers 5 mm Hg . Blood pressure decrease correlated with placebo BP ( P < .0005 , r = 0.53 to 0.70 ) . When corrected for placebo , target SBP ( < 140 mm Hg ) was reached in between 6 % to 15 % of patients on monotherapy . Sequential monotherapy achieved target in 29 % . Angiotensin converting enzyme inhibitors , calcium-blocking drugs , and diuretics had no more side effects than placebo . Patients on beta-blockers had more side effects and the well-being score was reduced . Diuretics and calcium-blocking drugs are more effective in elderly patients at lowering SBP pressure . beta-Blockers were relatively ineffective , were frequently contraindicated , and had more side effects . Monotherapy achieved control in only a small number of patients . In elderly people with essential hypertension , therapy should be instituted with diuretics or calcium-blocking drugs , but combination therapy will usually be required to achieve goal We studied the structural and functional characteristics of the vascular bed at calf level in 46 middle aged hypertensive patients ( 20 males and 26 females ) treated with different beta-blockers . After one week of placebo , the patients were divided into three groups : group 1 was treated with labetalol , an alpha-beta-blocker ( 200 mg t.t.d . ) ; group 2 was treated with acebutolol , a cardioselective beta-blocker with intrinsic sympathomimetic activity ( ISA ) ( 200 mg t.t.d . ) ; group 2 was treated with acebutolol , a cardioselective beta-blocker with intrinsic sympathomimetic activity ( ISA ) ( 200 mg t.t.d . ) ; group 3 was treated with metoprolol , a cardioselective beta-blocker without ISA ( 100 mg t.t.d . ) . Before and after placebo , and after three months of active drug treatment , we measured blood pressure , and rest and peak flow at the calf level by strain gauge plethysmography . Basal and minimal vascular resistances were calculated as the ratio between mean blood pressure and rest or peak flow , respectively . A significant decrease in blood pressure was observed in each group . However , basal and minimal vascular resistances decreased only in the labetalol-treated group . These observations indicate that antihypertensive agents that have similar effects on blood pressure , may have different effects on minimal vascular resistance . Therefore , maximum vasodilation of arterioles improves , suggesting that long term treatment with labetalol , but not with other beta-blockers is able to induce a partial regression of vascular structural alterations in hypertensive patients OBJECTIVE The aim was to examine the effects of a Mindfulness-Based Stress Reduction ( MBSR ) intervention on cardiovascular and cortisol activity during acute stress . METHOD Eighty-eight healthy community-dwelling individuals reporting elevated stress levels were r and omly assigned to the MBSR protocol or a waitlist control group . Before and after the intervention period they participated in a laboratory stress protocol consisting of mental arithmetic and speech tasks . Laboratory measurements included continuous cardiovascular parameters ( heart period , heart rate variability , and systolic and diastolic blood pressure [ SBP and DBP ] ) , and salivary cortisol . RESULTS Compared to the control group and controlling for age , sex , body mass index , and beta-blockers , the MBSR group showed larger pre- to postintervention decreases in overall SBP ( F(1 , 58 ) = 4.99 , p = .029 , partial η² = .08 ) and DBP ( F(1 , 58 ) = 11.09 , p = .002 , partial η² = .16 ) . In addition , the MBSR group exhibited smaller SBP and DBP stress-related changes from pre- to postintervention ( F(2 , 116 ) = 4.89 , p = .012 , partial η² = .08 ; F(2 , 116 ) = 6.07 , p = .007 , partial η² = .10 , respectively ) . No effects were obtained on other physiological measures . CONCLUSION MBSR may help reducing blood pressure levels and blood pressure reactivity to stress Objective : To compare the blood pressure‐lowering efficacy , the frequency of side effects and changes in laboratory values of three & bgr;‐blockers and a potassium‐sparing diuretic combination in elderly hypertensive patients . Design : The Swedish Trial in Old Patients with Hypertension ( STOP‐Hypertension ) was a prospect i ve , r and omized , double‐blind , multicentre trial comparing active antihypertensive treatment with placebo in patients aged 70‐84 years . Methods : The study group consisted of 1627 elderly hypertensive patients ( mean ± SD age 75.7 ± 3.7 years ; 37 % males , 63 % females ) . Supine and st and ing blood pressure , heart rate and side effects were recorded at each visit . Blood was drawn for routine analysis . The mean length of follow‐up was 25 months ( range 6‐65 ) . No patient was lost to follow‐up . Results : After 2‐months ' single‐drug therapy , all four active drugs were found to be equally effective in reducing diastolic blood pressure ( DBP ) . However , there were differences in their efficacy in reducing systolic blood pressure ( SBP ) ; the diuretic was significantly more effective than the & bgr;‐receptor blockers . The results of a series of multiple linear regression analyses showed that the observed differences in effect on SBP could not be explained by the different effects of the drugs on heart rate . More than two‐thirds of the patients were given supplementary treatment , most of them already by the 2‐month visit , after which there was no significant difference in blood pressure among the treatment regimens . The changes in laboratory values and in the prevalence of symptoms were minor for all four regimens . Conclusion : Metoprolol ( controlled release ) , atenolol , pindolol and the combination hydrochlorothiazide + amiloride were equally effective as single drugs in reducing DBP . There were differences in their efficacy in reducing SBP , the diuretic being more effective than the & bgr;‐blockers . After addition of supplementary treatment ( & bgr;‐blocker to diuretic , or vice versa ) there were no significant differences in blood pressure reduction among the groups . The changes in laboratory values and in the prevalence of symptoms were minor for all active treatment regimens . Thus , the satisfactory effect on cardiovascular morbidity and mortality was not impaired by low tolerability of the drugs Men aged 40 - 64 years with mild to moderate hypertension [ diastolic blood pressure ( DBP ) 100 - 130 mmHg ] were r and omized to treatment with a  diuretic ( n = 3272 ) or a  beta-blocker ( n = 3297 ) , with additional drugs if necessary , to determine whether a beta-blocker based treatment differs from thiazide diuretic based treatment with regard to the prevention of coronary heart disease ( CHD ) events and death .  Patients with previous CHD , stroke or other serious diseases , or with contraindications to diuretics or beta-blockers were excluded . If normotension ( DBP less than 95 mmHg ) was not achieved by monotherapy , other antihypertensive drugs were added , but the two basic drugs were not crossed over . Patients were assessed at 6-monthly intervals . The mean follow-up for end-points was 45.1 months . Blood pressure ( BP ) side effects and end-points were recorded in a st and ardized manner . Entry characteristics and the BP reduction achieved were very similar in both treatment groups . All analyses were made on an intention-to-treat basis . The incidence of CHD did not differ between the two treatment groups . The incidence of fatal stroke tended to be lower in the beta-blocker treated group than in the diuretic treated group . Total mortality and the total number of end-points were similar in both groups . The percentage of patients withdrawn due to side effects was similar , whereas the number of reported symptoms , according to a question naire , was higher for patients on beta-blockers . The incidence of diabetes did not differ between the two groups . Subgroup analyses did not detect a difference in the effect of beta-blockers compared with diuretics in smokers as opposed to non-smokers , and beta-blockers also had the same effects as diuretics in the quartile with the highest predicted risk for CHD . Beta-blockers and thiazide diuretics were approximately equally well tolerated . The two drugs had a similar BP reducing effect although additional drugs had to be given more often in the diuretic group . Antihypertensive treatment based on a beta-blocker or on a thiazide diuretic could not be shown to affect the prevention of hypertensive complications , including CHD , to a different extent A large-scale , 8-week , open-label , clinical experience trial evaluated the efficacy of the angiotensin II receptor ( AT1 subtype ) blocker c and esartan cilexetil ( 16 to 32 mg once daily ) either alone or as add-on therapy in 6465 hypertensive patients . The study population was 52 % female and 16 % African American with a mean age of 58 years . It included 5,446 patients who had essential hypertension ( HBP ) and 1,014 patients who had isolated systolic hypertension ( ISH ) . These patients had either untreated or uncontrolled hypertension ( systolic blood pressure [ SBP ] 140 to 179 mm Hg or diastolic blood pressure [ DBP ] 90 to 109 mm Hg inclusive at baseline ) despite a variety of antihypertensive medications including diuretics , calcium antagonists , angiotensin converting enzyme ( ACE ) inhibitors , and alpha- or beta-blockers , either singly or in combination . The mean baseline blood pressure for the HBP group was 156/97 mm Hg . C and esartan cilexetil as monotherapy ( in 51 % of HBP patients ) reduced mean SBP/DBP by 18.7/ 13.1 mm Hg . As add-on therapy ( in 49 % of HBP patients ) to various background therapies , c and esartan cilexetil consistently reduced mean SBP/DBP further , irrespective of the background therapy : diuretics ( 17.8/11.3 mm Hg ) , calcium antagonists ( 16.6/11.2 mm Hg ) , beta-blockers ( 16.5/ 10.4 mm Hg ) , ACE inhibitors ( 15.3/10.0 mm Hg ) , alpha-blockers ( 16.4/10.4 mm Hg ) . The mean baseline blood pressure for the ISH group was 158/81 mm Hg . C and esartan cilexetil , as monotherapy ( in 34 % of ISH patients ) , reduced SBP/DBP by 17.0/4.4 mm Hg . As add-on therapy ( in 66 % of ISH patients ) to various background therapies , c and esartan cilexetil consistently reduced mean SBP/DBP further , irrespective of the background therapy : diuretics ( 17.4/5.1 mm Hg ) , calcium antagonists ( 15.6/3.6 mm Hg ) , beta-blockers ( 14.0/4.8 mm Hg ) , ACE inhibitors ( 13.4/4.3 mm Hg ) , and alpha-blockers ( 11.6/4.5 mm Hg ) . The further blood pressure lowering effects of c and esartan cilexetil as add-on therapy were seen regardless of age , sex , and race . Overall , 6.8 % of the 6465 patients withdrew because of adverse events , most commonly headache ( 6.3 % ) and dizziness ( 5.0 % ) . Orthostatic hypotension was infrequent ; 0.2 % with c and esartan cilexetil alone , and 0.8 % with c and esartan cilexetil as add-on therapy . Thus , c and esartan cilexetil either alone or as add-on therapy was highly effective for the control of systolic or diastolic hypertension regardless of demographic background when used in typical clinical practice setting BACKGROUND AND OBJECTIVE In patients with chronic glomerular nephropathy associated arterial hypertension and proteinuria are considered to be cardinal risk factors in the progressive deterioration of renal function . Treatment regimens which reduce proteinuria and hypertension improve prognosis . The effect of the new beta-receptor blockers compared to common ACE-Inhibitors is of special interest . PATIENTS AND METHODS The studied cohort consisted of 11 patients with CGN , hypertension and proteinuria > 400 mg/24 h. Four drugs were given for 4 weeks , doubly blinded and r and omized according to a " Latin-square design " : Celiprolol ( beta-1-antagonist , beta-2-agonist , 200 mg/d ) , Atenolol ( selective beta-1-antagonist , 50 mg/d ) , Ramipril ( ACE-inhibitor , 2.5 mg/d ) and placebo . There was a two-week wash-out phase between each of the four treatment phases . At the end of each treatment phase glomerular filtration rate ( GFR ) and effective renal plasma flow ( ERPF ) were measured by inulin and para-amino-hippuric acid ( PAH ) clearance . Proteinuria was determined in the course of a three-day collection period at the end of each treatment phase . During this period blood pressures were measured with a continuous 24-hour blood pressure monitor . RESULTS Mean arterial blood pressure ( MAP ) was significantly reduced , compared with placebo , by all three antihypertensives ( 108 + /- 9 mm Hg with placebo , 98 + /- 12 mg Hg with atenolol , 101 + /- 11 mm Hg with celiprolol and 98 + /- 8 mm Hg with ramipril ; P < 0.01 ) . Celiprolol produced a significant rise In ERPF ( 322 + /- 109 ml/min with placebo , 391 + /- 110 ml/min with celiprolol : P < 0.05 ) . GFR was slightly , but not significantly , reduced by celiprolol and atenolol .  Filtration fraction remained unchanged with atenolol and celiprolol , while it was slightly , but not significantly , reduced with ramipril . Compared with the placebo , all three drugs significantly reduced proteinuria ( P < 0.05 ) : 1.8 + /- 1.3 g/24 h with placebo , 1.2 + /- 1.2 g/24 h with atenolol , 1.2 + /- 1.1 g/24 h with celiprolol and 1.4 + /- 1.4 g/24 h with ramipril . CONCLUSION These data indicate that , in addition to ACE inhibitors , the new generation of beta-receptor blockers in particular , because of their vasodilator action , favourably influence proteinuria and renal blood flow in patients with CGN and arterial hypertension Aerobic physical exercise is broadly recommended as a helpful adjunct to obtain blood pressure control in hypertension . Beta-blockade interacts with heart rate , sympathetic tone , maximal workload and local lactate production . In the present r and omized-controlled study , we compared the cardiovascular effects of an endurance training programme in elderly hypertensives with or without beta-blockers and developed a first approach to determine a lactate-based training heart rate in presence of beta-blockade . Fifty-two patients ( 23 with beta-blocker , 29 without beta-blocker ) ⩾60 years with systolic 24-h ambulatory blood pressure ( ABP ) ⩾140 mm Hg and /or antihypertensive treatment were r and omly assigned to sedentary activity or a heart-rate controlled 12-week treadmill exercise programme ( lactate 2.0 mmol/l ) . In the exercise group , the training significantly decreased systolic and diastolic 24-h ABP , blood pressure on exertion ( 100 W ) and increased endothelium-dependent vasodilation ( flow-mediated vasodilation , FMD ) and physical performance both in the presence and absence of beta-blockade ( P<0.05 each ) . The extent of ABP reduction did not significantly differ in the presence or absence of beta-blockade ( Δ systolic ABP 10.6±10.5 vs 10.6±8.8 mm Hg , Δ diastolic ABP 5.7±8.6 vs 5.8±4.0 mm Hg ) . Mean training heart rate was significantly lower in the patients on beta-blockers ( 97.2±7.7 vs 118.3±7.5/min , P<0.001 ) . Lactate-based aerobic endurance training evokes comparable cardiovascular benefits in the presence and absence of beta-blockade including a marked improvement of endothelial function . In the present study , target training heart rate with beta-blockers is about 18 % lower than without Purpose Tracheal extubation and emergence procedures induce abrupt changes in hemodynamics and humoral responses . We conducted a prospect i ve r and omized study to examine the effects of the short-acting beta-1 blocker , l and iolol , on hemodynamics during emergence from anesthesia in elderly patients with and without hypertension . Methods Thirty-one hypertensive and 32 normotensive elderly patients were r and omly divided into two groups : a control ( placebo group ) and a l and iolol infusion group . L and iolol was dissolved in 20 ml of saline and administered as an infusion at the rate of 0.125 mg·kg−1·min−1 for 1 min and then decreased to 0.04 mg·kg−1·min−1 until extubation . Control patients received an equal volume of saline . Heart rate and blood pressure were recorded every minute from immediately before the administration of l and iolol up to the discontinuation of l and iolol , and every 5 min from the discontinuation of l and iolol to 30 min after termination of the infusion . Results Systolic blood pressure in the control group patients with hypertension increased during anesthesia emergence and tracheal extubation , as did the heart rate . L and iolol infusion in the elderly patients with hypertension partially prevented the increase in systolic blood pressure and completely prevented the increase in heart rate associated with emergence from anesthesia . L and iolol infusion in the elderly patients without hypertension brought about a decrease in heart rate during emergence and tracheal extubation . Conclusion This study indicates that the use of a l and iolol infusion for preventing hemodynamic instability in elderly patients during the emergence period would be dependent on the presence or absence of hypertension in these patients BACKGROUND Although beta-blockers and angiotensin-converting enzyme ( ACE ) inhibitors are often used together , there is a lack of quantitative evidence for the efficacy of this combination in reducing  blood pressure ( BP ) .  OBJECTIVE The aim of this r and omized , double-blind , placebo-controlled , crossover study was to quantify the combined effect of a beta-blocker ( atenolol ) and an ACE inhibitor ( lisinopril ) in lowering BP . METHODS Participants who were > or = 40 years of age and enrolled in the hypertension or anticoagulation clinics at St. Bartholomew 's Hospital , London , United Kingdom , were r and omized to 3 consecutive 4-week treatments consisting of atenolol 25 mg plus placebo , lisinopril 5 mg plus placebo , and atenolol 25 mg plus lisinopril 5 mg , plus a period of 2 placebos . At the end of each period , seated BP was measured in the right arm using electronic monitors . RESULTS The mean  placebo-adjusted peak BP reductions among the 47 participants ( mean age , 62 [ range 42 - 82 ] years ; 75 % male ; 70 % white/30 % Asian ; mean baseline BP , 145/82 mm Hg ) who completed all 4 periods were significantly greater with the combination of both drugs than with either drug alone ( P < 0.001 ) . The systolic reductions were 22.9 mm Hg with combination treatment , 16.1 mm Hg with atenolol treatment , and 12.5 mm Hg with lisinopril treatment , and the diastolic reductions were 13.9 , 9.8 , and 6.8 mm Hg , respectively . The BP-lowering effect of the 2 drugs together was similar to that expected from the sum of each alone , allowing for the reduced effect of 1 drug given the lower pretreatment BP due to the other . The incremental systolic BP reduction from the 2 drugs together compared with 1 alone was 79 % ( 95 % CI , 54%-126 % ) of the expected additive effect , 88 % ( 95 % CI , 58%-130 % ) for diastolic BP , and 84 % ( 95 % CI , 65%-118 % ) for the mean of systolic and diastolic BP . CONCLUSIONS The combination of the beta-blocker atenolol 25 mg plus the ACE inhibitor lisinopril 5 mg was associated with a significantly greater decrease in BP compared with either alone . The BP reduction with the combination treatment was similar to and statistically consistent with the 2 drugs having additive effects . Clinical Trials Identification Number : IS RCT N97280940 OBJECTIVES To evaluate if magnesium alters blood pressure in hypertensive patients treated with beta blockers and if such effect can be coupled to a change in potassium and magnesium levels in muscle , serum and urine . DESIGN A r and omized double-blind , cross-over study with magnesium and placebo taken orally , each for 8 weeks . SETTING Outpatient clinic , University Hospital , Umeå , Sweden . SUBJECTS Thirty-nine patients aged 26 - 69 years with moderate essential hypertension , treated before entry and during the study with continuous , unchanged beta blockers completed the study . INTERVENTIONS R and om allocation to receive magnesium aspartate or placebo . Daily magnesium dose was 15 mmol ( 365 mg ) distributed three times a day over 8 weeks . MAIN OUTCOME MEASURES Blood pressure , serum , urine and muscle magnesium and potassium . Measurements performed at the start , after 8 and 16 weeks . RESULTS Systolic supine and st and ing blood pressure significantly decreased when magnesium was supplemented following placebo but not when magnesium was given at start . When magnesium and placebo groups were independently compared there was no significant change in supine and st and ing systolic and diastolic pressure . Serum and urine magnesium and serum potassium were significantly higher after magnesium treatment , whilst no change was present in urine potassium or in muscle magnesium and potassium . CONCLUSIONS This study showed that 15 mmol magnesium day-1 given to mild to moderate hypertensive patients treated with beta blockers could be the cause of a significant decrease in supine and st and ing systolic blood pressure OBJECTIVE To evaluate the efficacy of the monotherapy of 15 agents in treating essential hypertension . METHODS After 2-week wash-out , a total of 370 patients with seated diastolic blood pressure 95 - 114 mmHg and seated systolic blood pressure < 180 mmHg were r and omized to different therapeutic groups .  24-hour ambulatory blood pressure monitoring was performed before medication and at the end of 8 weeks . RESULT All the agents significantly reduced the 24 hour mean blood pressures after treatment except doxazosin , terazosin , and torasemide . CONCLUSION The result suggested that the angiotensin-converting enzyme inhibitors , angiotensin II receptor blockers , beta-blockers and long-acting calcium antagonists were effective in treating essential hypertension , while the low-dose doxazosin , terazosin and torasemide can be used for combination therapy but not for monotherapy
Pindolol , celiprolol and alprenolol  lowered SBP and DBP compared to placebo .
Acebutolol  lowered SBP but there was no clear evidence that it lowered DBP .
There was no clear evidence that pindolol and  oxprenolol lowered SBP or DBP .
Higher dose partial agonists did not appear to provide additional BP lowering effects compared to lower dose .
There was no evidence of a greater effect at doses higher than the initial doses .
Based on the indirect comparison of the results in this review and two Cochrane review s on angiotensin-converting-enzyme ( ACE ) inhibitors and angiotensin receptor blockers ( ARBs ) , which also used similar inclusion criteria as this review , the BP lowering effect appeared to be less than the effect in patients with mild to moderate elevated BP who were taking ACE inhibitors  and ARBs based on an indirect comparison .
Withdrawals due to adverse effects were only reported in one trial so it is impossible to assess the harm of these drugs
BACKGROUND Partial agonists are a subclass of beta blockers used to treat hypertension in many countries .
Partial agonist act by stimulating beta receptors when they are quiescent and blocking beta receptors when they are active .
The blood pressure ( BP ) lowering effect of partial agonist beta blockers has not been quantified .
OBJECTIVES To quantify the dose-related effects of various partial agonists beta blockers on systolic blood pressure ( SBP ) , diastolic blood pressure ( DBP ) and heart rate versus placebo in patients with primary hypertension .