Effects of hydrochlorothiazide, diltiazem and enalapril on mononuclear cell sodium and magnesium levels in systemic hypertension

Sixteen patients (mean age 68 years) with mild to moderate hypertension were treated with either diltiazem or hydrochlorothiazide for 6 weeks, followed by enalapril for a further 6 weeks. A second group of 40 patients (mean age 71 years) was treated with either hydrochlorothiazide or enalapril for 12 weeks; nonresponders received both drugs for 8 weeks. Treatment with hydrochlorothiazide or enalapril resulted in a lowering of systolic and diastolic blood pressures, but diastolic pressure was lower in patients treated with enalapril (89 +/- 2 and 82 +/- 2 mm Hg, respectively; p less than 0.05). Treatment with diltiazem resulted in a decrease in diastolic pressure only. Treatment with hydrochlorothiazide resulted in a 17% decrease in serum potassium (p less than 0.05), which returned to normal when enalapril was substituted. Hydrochlorothiazide also produced a 23% decrease in mononuclear cell sodium content at 4 weeks (p less than 0.01), with a further 15% decrease at 12 weeks (p less than 0.05). Mononuclear cell potassium and magnesium also decreased at 12 weeks by 18 and 16%, respectively (p less than 0.05). All these effects were reversed when enalapril was substituted. A similar pattern of events was seen with diltiazem, which was again reversed with enalapril. Finally, there was no relation between changes in mononuclear cell sodium or other cation content and changes in blood pressure.     

Comparative effects of diltiazem and hydrochlorothiazide in blacks with systemic hypertension

The blood pressure-lowering effects of a calcium-entry blocker, diltiazem (240 or 360 mg/day), and a thiazide diuretic, hydrochlorothiazide (50 or 100 mg/day), were studied in 20 black hypertensive patients. Supine blood pressure decreases of -34/-18 mm Hg for diltiazem and -29/-21 mm Hg for hydrochlorothiazide were noted after 14 weeks of therapy. Differences between drugs were not significant. Blood pressures were normalized in all 4 of the monotherapy nonresponders when the 2 drugs were combined. Significant adverse effects were not noted. These data suggest that diltiazem is an effective antihypertensive agent in black patients. As monotherapy, its blood pressure-lowering effect is equivalent to hydrochlorothiazide.     

Comparison of hydrochlorothiazide and sustained-release diltiazem for mild-to-moderate systemic hypertension

The safety and efficacy of sustained-release diltiazem, 120 to 180 mg twice daily, was compared with those of hydrochlorothiazide, 25 to 50 mg twice daily, in 207 patients with mild-to-moderate hypertension (supine diastolic blood pressure [BP] 95 to 114 mm Hg) using a baseline, placebo, parallel-design study protocol. All patients received placebo for 2 to 4 weeks, followed by either study drug during the double-blind phase, titrated over 8 weeks to achieve a goal of supine diastolic BP reduction of at least 10 mm Hg and/or a diastolic BP of less than 90 mm Hg. Patients not achieving the treatment goal with either drug alone received the other drug in combination. Both drugs produced significant decreases in supine and upright BP throughout the 26-week study. The magnitude of decrease in mean supine diastolic BP was similar for both drugs as monotherapy at week 14 (-11.4 and -12.1 mm Hg, respectively). Hydrochlorothiazide produced significantly greater reductions at week 14 in mean supine systolic BP than sustained-release diltiazem (-19.5 and -12.7 mm Hg, respectively). The difference in mean supine diastolic BP reduction with the 2 drugs diminished when hydrochlorothiazide (50 mg/day) was compared with sustained-release diltiazem. The BP effects were sustained for 6 months with both drugs. The 2 drugs appeared to lower BP more in patients older than 60 years and more in black than in white patients. The combination of the 2 drugs decreased supine diastolic BP to goal levels in about 56% of the patients not achieving goal with either drug alone. Adverse effects were minimal with either drug alone and in combination, except for hypokalemia, which increased with thiazide alone and in combination.     

Antihypertensive therapy with diltiazem and comparison with hydrochlorothiazide

Fourteen hypertensive patients with a mean sitting systolic and diastolic blood pressure (BP) of 153 +/- 16/100 +/- 4 mm Hg were treated successively with hydrochlorothiazide and diltiazem for 8 weeks each. The BP response and changes in heart rate, left ventricular size and function, and plasma catecholamine concentrations and renin activity were monitored. The 2 drugs had comparable antihypertensive effects, with mean decreases of 14, 9 and 11 mm Hg for the sitting, standing and supine diastolic BP, respectively, during hydrochlorothiazide treatment and mean decreases of 16, 18 and 12 mm Hg during diltiazem treatment. Heart rate was unchanged, although plasma norepinephrine concentrations increased significantly during diltiazem treatment. Plasma renin activity increased slightly, from 0.6 to 0.9 ng/ml/hour during diltiazem treatment, but the change was not significant (p less than 0.10). Left ventricular ejection fraction and end-diastolic volume were not affected by either agent. In conclusion, diltiazem is an effective antihypertensive agent, which because of its benign side effect profile, may be useful as a step 1 agent.     

Diuretics versus calcium-channel blockers in systemic hypertension: a preliminary multicenter experience with hydrochlorothiazide and sustained-release diltiazem

The safety and efficacy of sustained-release diltiazem 120 to 180 mg, 2 times a day, were compared with hydrochlorothiazide 25 to 50 mg, 2 times a day, and the combination of diltiazem and hydrochlorothiazide in 56 patients with mild to moderate hypertension (supine diastolic blood pressure between 95 and 114 mm Hg) using a placebo-controlled, parallel-design protocol. Data from an additional 21 patients were evaluated for safety only. The data reported herein represent the preliminary experience from a larger 200-patient multicenter study. All patients received placebo for 4 weeks, followed by either hydrochlorothiazide or diltiazem titrated to achieve a diastolic blood pressure reduction of greater than or equal to 10 mm Hg to reach a goal supine diastolic blood pressure of less than 90 mm Hg. Patients not achieving the treatment goal received hydrochlorothiazide plus diltiazem. At week 14, on maintenance monotherapy, diltiazem and hydrochlorothiazide produced comparable reductions in blood pressure from placebo baseline (160.3 +/- 24.3/101.7 +/- 5.5 to 145.2 +/- 24.1/89.8 +/- 7.4 mm Hg with diltiazem, 156.0 +/- 15.6/103.7 +/- 4.7 to 134.1 +/- 12.5/89.2 +/- 9.5 mm Hg with hydrochlorothiazide, p less than 0.001 for both). Diltiazem and hydrochlorothiazide achieved goal blood pressure in 42% and 45% of patients, respectively. The effects in responders were sustained for 6 months. In patients who did not achieve the treatment goal, 63% responded to diltiazem plus hydrochlorothiazide.No clinically significant postural hypotension was observed on any regimen. Heart rate was slightly lower with diltiazem than with hydrochlorothiazide. Adverse effects were minimal with diltiazem, hydrochlorothiazide and diltiazem plus hydrochlorothiazide but more hypokalemia occurred with hydrochlorothiazide.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of diltiazem and hydrochlorothiazide for treatment of patients 60 years of age or older with systemic hypertension

This randomized, double-blind, parallel design trial compared the efficacy and safety of monotherapy with either sustained-release diltiazem or hydrochlorothiazide in 61 men greater than or equal to 60 years of age with a diastolic blood pressure (BP) between 94 and 104 mm Hg. BP, heart rate, laboratory blood and urine tests, left ventricular wall thickness and mass index (as estimated by M-mode echocardiography) and rate and type of ventricular premature complexes (via ambulatory electrocardiographic monitoring) were determined before, during and after drug treatment. Both drugs produced highly significant (p less than 0.001) decreases in supine and upright systolic and diastolic BP. The mean dosages of diltiazem and hydrochlorothiazide used were 260 and 52 mg/day, respectively; at these dosages, 80% of diltiazem-treated versus 71% of hydrochlorothiazide-treated patients achieved goal reduction in BP (supine diastolic BP reduction of greater than 10 mm Hg and to less than 90 mm Hg). Both drugs were well tolerated, although hydrochlorothiazide therapy was associated with multiple biochemical abnormalities not seen with diltiazem. Neither drug affected left ventricular mass index or the rate of ventricular ectopic activity. Diltiazem and hydrochlorothiazide are both effective and safe agents when used as monotherapy in older patients with systemic hypertension unaccompanied by other clinically significant cardiovascular disease.     

Effects of diltiazem on cardiovascular responses during exercise in systemic hypertension and comparison with propranolol

Sixteen patients with uncomplicated systemic hypertension were treated with placebo, diltiazem (180 mg/day) and propranolol (60 mg/day) for 1 month each. Each patient performed multistage symptom-limited treadmill exercise tests during each period of administration. There was no significant difference in maximal exercise duration between placebo, diltiazem and propranolol. Diltiazem significantly decreased both systolic and diastolic blood pressure (BP) and heart rate at rest, during submaximal exercise at the same work load and maximal exercise. Propranolol produced similar changes in systemic BP and heart rate at rest and during exercise. However, the reductions in systolic BP, heart rate and pressure-rate product with diltiazem during exercise were smaller than those with propranolol at small doses, suggesting that diltiazem in its usual therapeutic dose was almost devoid of beta-blocking activity. Thus, diltiazem may be of benefit to hypertensive patients because it reduces systemic BP even during exercise. It is particularly useful when systemic hypertension occurs in association with coronary artery disease because of its effects of coronary artery dilatation and heart rate reduction.     

A dose escalation trial comparing the combination of diltiazem SR and hydrochlorothiazide with the monotherapies in patients with essential hypertension.

A multicentre, randomised, placebo-controlled parallel group study comparing various doses of the combination diltiazem SR (DTZ SR)/hydrochlorothiazide (HCTZ) with the monotherapies was performed to delineate the optimal antihypertensive dosage of the two drug combinations. The study was carried out in 298 patients with mild to moderate essential hypertension (stable supine diastolic blood pressure, DBP, greater than or equal to 95 and less than or equal to 110 mmHg). After a single-blind placebo lead-in period lasting 4-6 weeks to establish stable baseline BP, the patients were randomised to receive either placebo (n = 75), HCTZ (n = 76), DTZ SR (n = 72), or the combination of DTZ SR/HCTZ (n = 75). There were three 4-week evaluation periods with forced escalation of therapy as follows: HCTZ (6.25, 6.25, 12.5 mg twice daily), DTZ SR (60, 90, 120 mg twice daily), and the combination of DTZ SR/HCTZ (60/6.25, 90/6.25, 120/12.5 mg twice daily). DTZ SR/HCTZ (120/12.5 mg) produced statistically significantly greater reductions in supine DBP compared with each monotherapy and placebo. The lower doses of DTZ SR/HCTZ (60/6.25 mg and 90/6.25 mg) produced statistically significantly greater supine DBP reductions compared with DTZ SR monotherapy and placebo, but not compared with HCTZ monotherapy. A comparison of reduction in supine DBP between evaluation periods demonstrated a dose-response relationship for the combination therapy in reducing BP over the dosage range studied. Adverse clinical and laboratory events were not significantly different between the therapies.(ABSTRACT TRUNCATED AT 250 WORDS)     

Candesartan and hydrochlorothiazide in isolated systolic hypertension

AIM: We investigated the efficacy and safety of daily candesartan 8/16mg and hydrochlorothiazide 12.5 mg as monotherapy and in combination in older patients with systolic hypertension. METHODS: The study used a double-blind randomized placebo-controlled crossover design. Treatment phases were of 6 weeks duration. For inclusion, patients were aged 55-84 years with sitting systolic blood pressure (SBP) 160-210 mmHg and diastolic blood pressure (DBP) < 95 mmHg. Nineteen patients (11 male, eight female, median age 68 years) completed the study. MAJOR FINDINGS: Compared with the placebo phase, clinic and ambulatory SBP was significantly reduced with both dose-adjusted candesartan and fixed-dose hydrochlorothiazide as monotherapy, the effect of candesartan being greater than that of hydrochlorothiazide. In combination, the effects of the two drugs were additive. Both drugs were well tolerated either as monotherapy or in combination. CONCLUSION: Both candesartan and a low dose of hydrochlorothiazide are effective and well-tolerated antihypertensive agents in isolated systolic hypertension with additive effects in combination. Candesartan was more effective than hydrochlorothiazide, although it is possible that dose adjustment only of candesartan could have enhanced its relative effectiveness.     

Effects of gender and age on the cardiac baroreceptor reflex in hypertension.

The present study examined whether alterations in the cardiac baroreceptor reflex in hypertension may be a function of constitutional differences associated with gender and age. These hypotheses were tested using a cross-sectional design that compared 20 normotensive and 21 hypertensive men and women of varying age for differences in baroreceptor reflex sensitivity and response latency for heart rate, obtained using a modified bolus phenylephrine (Oxford) method. Relative to their respective normotensive controls, baroreceptor reflex sensitivity was reduced in hypertensive men, but not in hypertensive women. Among normotensive subjects, men had greater baroreceptor reflex sensitivity than women. Independent from the effects associated with differences in blood pressure, age was not a significant predictor of reduction in baroreceptor reflex sensitivity. However, a combination of high blood pressure and older age was associated with a significant increase in baroreceptor reflex response time. In summary, gender and aging interacted with hypertension to alter two different aspects of the baroreceptor reflex. These results provide a preliminary indication that a decline in arterial baroreflex sensitivity may be more specific to hypertension in men than in women. Prolongation in baroreflex response latency in older hypertensive subjects also suggested that aging and hypertension may have a synergistic effect on cardiac parasympathetic function.     

Effects of reduction in dose and discontinuation of hydrochlorothiazide in patients with controlled essential hypertension

We studied the effects of a reduction in dose of hydrochlorothiazide from 50 to 25 mg/d, and its discontinuation for up to 22 months in 36 well-controlled hypertensive patients. Hydrochlorothiazide was discontinued if the diastolic blood pressure remained less than or equal to 94 mm Hg after a 6-month period on the lower dose of hydrochlorothiazide. No other changes were made in medications or diet. Sitting systolic blood pressure rose from 135 +/- 15 mm Hg to 140 +/- 14 mm Hg on reduction of the hydrochlorothiazide dose and rose still further to 145 +/- 20 mm Hg on discontinuation. Even greater increases in standing blood pressure were observed. There were no significant effects on the diastolic blood pressure with reduction of dose or discontinuation of hydrochlorothiazide. A significant decrease in the serum uric acid and a rise in serum potassium occurred. There were no changes in serum glucose or lipids on reduction in the dose of hydrochlorothiazide; whereas, with discontinuation, the serum lipids and hemoglobin A1C fell significantly. These results suggest that the benefits of a reduced dose of hydrochlorothiazide may not be as great as considered heretofore.     

Effects of diltiazem on hemodynamics, plasma catecholamine and renin activity during exercise in hypertension]

The effects of diltiazem on hemodynamics, plasma catecholamine and plasma renin activity were studied during treadmill exercise test in 9 cases with moderate essential hypertension. Diltiazem of 120 mg/day was orally administered for 4 weeks. At maximum exercise, significant decrease in systolic blood pressure (-32 mmHg), heart rate (-16/min), pressure-rate product (-7,883 mmHg/min), plasma norepinephrine (-195 ng/L) and plasma epinephrine (-11 ng/L) were observed; while, diastolic blood pressure, ST depression and plasma renin activity showed no significant change. Also, a significant correlation between systolic blood pressure and plasma norepinephrine (r = 0.57, p < 0.001), especially after diltiazem therapy (r = 0.68, p < 0.001), was observed. These findings indicated that diltiazem can reduce the secretion of catecholamine from the sympathetic nerves during exercise in patients with essential hypertension.     

Ketanserin and hydrochlorothiazide in the treatment of arterial hypertension

The chronic antihypertensive effect of the combination of ketanserin (KET) 40 mg + hydrochlorothiazide (HCTZ) 12.5 mg was evaluated in 20 patients with arterial hypertension of mild to moderate degree. After a 2-week wash-out period, patients were prescribed a single oral dose of KET 40 mg or HCTZ 25 mg in a randomized order at 2-day intervals and blood pressure and heart rate were measured during the following 24 hrs by an automatic recorder. Thereafter patients were given the combination of KET 40 mg + HCTZ 12.5 mg for 6 weeks and 24 hrs blood pressure was recorded after the first dose of the combination and at the end of treatment. Ketanserin induced a significant fall in systolic and diastolic pressures for up to 8 hrs; thiazide did not induce any change in these parameters. The combination of KET + HCTZ in the acute study reduced significantly systolic (SBP) and diastolic (DBP) blood pressures for up to 10 hrs. After 6 weeks of treatment with KET + HCTZ, blood pressure showed a further fall at each time period and was normalized (BP greater than 160/80 mmHg) for 8 hrs after dosing. The results of this study indicate that once daily oral administration of the combination of KET 40 mg + HCTZ 12.5 mg in mild to moderate primary hypertensives significantly reduces blood pressure over 24 hrs. Fairly good control of BP, i.e. BP less than 160/90 mmHg, was, however, achieved only up to 8 hrs after drug administration, indicating that this combination given once daily is not able to normalize BP over the following 24 hrs.     

Enhanced hypoxic pulmonary vasoconstriction in hypertension

In this study, we tested the hypothesis that hypoxic pulmonary vasoconstriction may be enhanced in systemic hypertension. The hypothesis took origin from the following two considerations: alveolar hypoxia constricts the pulmonary vessels by enhancing the Ca2+ penetration across sarcolemma of the smooth muscle cells and systemic high blood pressure is associated with an elevation of tone and reactivity of the lung vessels, which seems to depend on an excessive cytosol free Ca2+ concentration due to alterations in sodium handling and in the Na+-Ca2+ exchange system. These considerations suggest the possibility that the disorders in the biochemistry of smooth muscle contraction in hypertension facilitate the rise of cytosol Ca2+ concentration during alveolar hypoxia, thus resulting in a potentiation of the vasoconstrictor properties of this stimulus. In 43 hypertensive and 17 normotensive men, pulmonary arteriolar resistance has been evaluated during air respiration and after 15 minutes of breathing 17%, 15%, and 12% oxygen in nitrogen. Curves relating changes in pulmonary arteriolar resistance to oxygen breathing contents had similar configuration in the two populations but in hypertension were steeper and significantly shifted to the left, reflecting a lower threshold and an enhanced reactivity. This pattern was not related to differences in severity of the hypoxic stimulus, plasma catecholamine concentration, or hypocapnia and respiratory alkalosis induced by hypoxia and probably was not mediated through alpha-receptor activation. Calcium channel blockade with nifedipine was able to almost abolish both the normotensive and the hypertensive pulmonary vasoconstriction reaction. These findings support the hypothesis that hypoxic pulmonary vasoconstriction may be enhanced in systemic hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)     

Renal effects of diltiazem in primary hypertension

Although the calcium channel blocker diltiazem has been shown to be an effective antihypertensive agent, its effect on renal function, salt and water excretion, and body fluid composition has not been well characterized in patients with primary hypertension. Therefore, these parameters were prospectively studied in 18 subjects with primary hypertension after placebo and 8 weeks of diltiazem monotherapy. Diltiazem monotherapy was confirmed to be an effective antihypertensive agent. Although mean arterial pressure was reduced from 121 to 108 mm Hg, diltiazem had no overall effect on glomerular filtration rate, renal plasma blood flow, salt and water excretion, or body fluid composition. Renal vascular resistance, however, was decreased. In subjects with pretreatment glomerular filtration rates of 80 ml/min/1.73 m2 or less, diltiazem therapy was associated with marked improvement in glomerular filtration rate (48%) and effective renal plasma flow (36%). Since the filtration fraction was unchanged, changes in glomerular filtration rate may have been related to the attenuated intrarenal effects of angiotensin II or norepinephrine, or both.     

A comparative study on the effectiveness of losartan/hydrochlorothiazide and telmisartan/hydrochlorothiazide in patients with hypertension

Purpose: Long-term effects of a low-dose hydrochlorothiazide (HCTZ) with losartan (LOS) on uric acid (UA) metabolism as well as glucose metabolism have been studied in hypertensive patients in comparison with those of a low-dose HCTZ with telmisartan (TEL).

Method: Fifty-nine hypertensive patients were allocated to a combination therapy with either losartan (50?mg/day)/HCTZ (12.5?mg/day) (LOS?+?HCTZ group: n?=?37) or telmisartan (40?mg/day)/HCTZ (12.5?mg/day) (TEL?+?HCTZ group: n?=?22), respectively. Before and 1 year after the treatment, blood pressure and biochemical parameters of blood and urine were evaluated.

Results: Both systolic and diastolic blood pressures significantly decreased in two groups, without any statistical differences among them. LOS?+?HCTZ caused no changes in the serum UA level or the ratio of UA clearance to creatinine clearance (CUA/Ccr), whereas TEL?+?HCTZ significantly increased the serum UA level and reduced CUA/Ccr. LOS?+?HCTZ did not influence CUA/Ccr in patients with their serum UA below 5.4?mg/dl, while LOS?+?HCTZ significantly increased CUA/Ccr in patients with their serum UA above 5.5?mg/dl. TEL?+?HCTZ significantly reduced CUA/Ccr in patients with their serum UA below and above 5.4?mg/dl to increase serum UA level significantly. Neither combination therapies caused any changes in fasting plasma glucose, HbA1c and HOMA-R. In patients with their serum UA level above 5.4?mg/dl, TEL?+?HCTZ increased HOMA-R, whereas LOS?+?HCTZ did not.

Conclusions: LOS?+?HCTZ did not influence UA metabolism as well as glucose metabolism, likely because of inhibitory action of losartan on URAT1, although TEL?+?HCTZ were accompanied with impairment of the UA metabolism and glucose metabolism.     

Two forms of vasoconstriction in systemic hypertension

Clinical, pharmacologic and biochemical evidence characterizes essential hypertension as a heterogeneous spectrum of pathophysiologic substances rather than the single entity it has long been presumed to be. Although the causes of essential hypertension remain obscure, 2 different mechanisms for long-term vasoconstriction that sustain diastolic hypertension in the experimental and clinical forms of primary aldosteronism and renovascular hypertension can also be identified and quantified among patients with essential hypertension. The first mechanism is renin independent, requires antecedent sodium retention and appears related to abnormal membrane transport of calcium. This vasoconstriction is identified by low plasma renin and ionized calcium and is correctable by sodium depletion or calcium channel or alpha blockade. The second vasoconstrictor mechanism is renin mediated and involves an increase in cytosolic calcium. This mechanism is quantifiable by the plasma renin level or the hypotensive response to an antirenin-system drug (converting enzyme inhibitor, beta blocker or saralasin). Depending on the state of sodium balance, these 2 mechanisms contribute reciprocally to maintenance of arteriolar tone in experimental models, in both normal and hypertensive people, and in patients with congestive heart failure. In these situations, at the extremes of the range of plasma renin values, one or the other mechanism predominates, whereas in the medium range of renin values both mechanisms can be operative. These interrelations provide a basis for applying more precisely tailored therapy and for stratifying patients pathophysiologically for further study.     

Effects of diltiazem retard on ambulatory blood pressure and heart rate variability in patients with essential hypertension

BACKGROUND: Dihydropyridine calcium antagonists increase heart rate due to reflex activation of the sympathetic nervous system, although these effects are less obvious for long-acting agents. OBJECTIVE: To study the effects of diltiazem retard, a long-acting nondihydropyridine calcium antagonist, on 24h blood pressure, heart rate and autonomic nerve activity in patients with essential hypertension. DESIGN: Randomized crossover design. METHODS: Thirteen patients [five men and eight women, aged 64+/-2 years (mean+/-SEM)] were administered placebo or diltiazem retard (100-200mg once daily) for 4 weeks each. Ambulatory monitoring of blood pressure and heart rate, and electrocardiography were carried out at the end of each period using a multibiomedical recorder (TM-2425). Autonomic nerve activity was evaluated by power spectral analysis of variability of heart rate using the high-frequency component as an index of parasympathetic nerve activity and the ratio of the low-frequency component and the high-frequency component as an index of sympathovagal balance. RESULTS: Treatment with diltiazem retard significantly decreased 24h average blood pressure and heart rate by 11.6+/-3.6/5.7+/-1.8mmHg and 5.0+/-1.1 beats/min, respectively. The changes in daytime and night-time values were comparable. Diltiazem retard also significantly decreased daytime and 24h low:high-frequency-component ratio (2.0+/-0.2 versus 1.7+/-0.2 and 1. 8+/-0.2 versus 1.6+/-0.2, respectively). CONCLUSIONS: These results indicate that diltiazem retard is effective as a once-daily antihypertensive agent and has favorable effects on heart rate and the autonomic nervous system.     

Comparison of nitrendipine and hydrochlorothiazide for systemic hypertension

Left ventricular (LV) hypertrophy with associated LV systolic and diastolic dysfunction is frequently found in patients with systemic hypertension, and is multifactorial in origin. Although a reduction in blood pressure (BP) often results in regression of hypertrophy, the pharmacologic profiles of the antihypertensive agents used may determine the probability of such regression despite similar levels of BP reduction. Thiazide diuretic drugs may actually result in increased LV hypertrophy; calcium channel antagonists may cause regression or no change. The effects of treatment with nitrendipine (20 mg/day) or hydrochlorothiazide (50 mg/day) were compared in an 8-week, double-blind study of 18 hypertensive subjects aged 50 years or older. BP was significantly reduced (p less than 0.05) by both nitrendipine (from 161 +/- 29/102 +/- 4 to 145 +/- 24/92 +/- 7 mm Hg; mean +/- standard deviation) and hydrochlorothiazide (from 162 +/- 15/105 +/- 6 to 143 +/- 20/95 +/- 7 mm Hg). Plasma norepinephrine increased in the nitrendipine group, from 202 +/- 110 to 332 +/- 220 pg/ml at 8 weeks of therapy and in the hydrochlorothiazide group, from 147 +/- 130 to 313 +/- 277. Plasma renin activity changed from 3.2 +/- 2.4 to 3.5 +/- 2.1 during nitrendipine treatment, but from 2.1 +/- 2.1 to 10.5 +/- 10.8 ng angiotensin l/ml/90 min (p less than 0.05) during treatment with hydrochlorothiazide. Left ventricular mass index did not change significantly with either therapy.(ABSTRACT TRUNCATED AT 250 WORDS)