Enalapril In Essential Hypertension Research Articles

Endothelial nitric oxide synthase tagSNPs influence the effects of enalapril in essential hypertension

The antihypertensive effects of angiotensin-converting enzyme inhibitors (ACEi) are associated with up-regulation of endothelial nitric oxide synthase (NOS3) activity. This mechanism may explain how polymorphisms in NOS3 gene affect the antihypertensive responses to ACEi. While clinically relevant NOS3 polymorphisms were previously shown to affect the antihypertensive responses to enalapril, no study has tested the hypothesis that NOS3 tagSNPs influence the antihypertensive effects of this drug. We examined whether the NOS3 tagSNPs rs3918226, rs3918188, and rs743506, and their haplotypes, affect the antihypertensive responses to enalapril in 101 patients with essential hypertension. Subjects were prospectively treated only with enalapril for 8 weeks. Genotypes were determined by Taqman® allele discrimination assay and real-time polymerase chain reaction (PCR) and haplotype frequencies were estimated. We compared the effects of NOS3 tagSNPs on changes in blood pressure after enalapril treatment. To confirm our findings, multiple linear regression analysis was performed adjusting for age, gender, ethnicity, and alcohol consumption. We found that hypertensive patients carrying the AA genotype for the tagSNP rs3918188 showed lower decreases in blood pressure in response to enalapril. Moreover, the TCA haplotype was associated with improved decreases in blood pressure in response to enalapril compared with the CAG haplotype. Adjustment for covariates in multiple linear regression analysis did not change these effects. In addition, when patients were stratified according to the dose of enalapril used, we found that the carries of the T allele for the functional tagSNP rs3918226 showed more intense decreases in blood pressure in response to enalapril 20 mg/day. Our findings suggest that NOS3 tagSNPs influence the effects of enalapril in essential hypertension.

Comparative Renal and Cardiac Effects of Tertatolol and Enalapril in Essential Hypertension

The influence of a 3-month antihypertensive treatment on cardiac structure and renal function was assessed in patients with uncomplicated essential hypertension randomly allocated to treatment by the nonselective beta-blocker tertatolol or the angiotensin-converting enzyme inhibitor enalapril. Both tertatolol and enalapril treatments were associated with a similar decrease in mean arterial pressure (-26 +/- 6 and -15 +/- 2 mm Hg, respectively, both p < 0.05 in comparison with baseline values) and left ventricular mass (echocardiography: -48 +/- 17 vs. -18 +/- 6 g) but no change in glomerular filtration rate (DTPA clearance). Renal vascular resistance decreased similarly in both groups. Urinary albumin excretion was not significantly modified in either group. These results indicate that a consistent reduction in arterial pressure by either treatment was associated with a proportional change in left ventricular geometry and no alteration in renal function.

A Comparative Study of the Effects of Nitrendipine and Enalapril in Essential Hypertension

In this study, we compared the effects of nitrendipine (20-40 mg daily) and enalapril (20-40 mg daily) in 44 patients with mild to moderate essential hypertension. After a 4-week placebo period, the patients entered a double-blind, crossover study of 16 weeks, divided by a second 4-week placebo period. Sitting and standing blood pressures (standard mercurymeter) were measured every 2 weeks. Ten patients dropped out, so 34 patients were evaluable. Two patients dropped out because of surgery, one patient was withdrawn because of accelerating hypertension, and seven patients discontinued because of side effects (two on placebo, four on enalapril, and one on nitrendipine). Sitting blood pressures decreased from 172 +/- 3/107 +/- 1 to 159 +/- 3/94 +/- 1 mm Hg on nitrendipine (p less than 0.001) and to 157 +/- 4/96 +/- 2 mm Hg on enalapril (p less than 0.001). The heart rate did not change. Both compounds had no significant effect on serum lipids and on renal function. With regard to side effects, flushing occurred in 10 patients on nitrendipine and in 3 on enalapril (p less than 0.05); cough was noted in 3 patients on enalapril. When using a diastolic pressure less than 95 mm Hg as a response, 72% responded on nitrendipine and 64% on enalapril (n.s.). In conclusion, nitrendipine and enalapril, given as monotherapy, were equally effective antihypertensive agents in this group of patients with uncomplicated, moderate, essential hypertension. The use of either of the tested agents seems to be more limited by its specific side effects than the lack of antihypertensive efficacy.

Efficacy and Safety of a New Angiotensin-Converting Enzyme Inhibitor, Ramipril, vs. Enalapril in Essential Hypertension

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A Comparative Study of the Effects of Nitrendipine and Enalapril in Essential Hypertension

A Comparative Study of the Effects of Nitrendipine and Enalapril in Essential Hypertension

Efficacy and Safety of a New Angiotensin-Converting Enzyme Inhibitor, Ramipril, vs. Enalapril in Essential Hypertension

The antihypertensive effect of ramipril, a new angiotensin-converting enzyme (ACE) inhibitor, was evaluated and compared to enalapril in a double-blind, randomized, controlled trial. Subjects received either 2.5, 5, or 10 mg of ramipril given once daily or 5, 10, or 20 mg of enalapril once daily for 4 weeks. Significant decreases from baseline in supine and standing diastolic blood pressures were seen in all dosage groups at end point. There were significant decreases at end point for supine and standing systolic blood pressures at the higher doses. Side effects were minimal and were similar for all treatment groups.

Efficacy of enalapril in essential hypertension and its comparison with atenolol

The effect of enalapril was evaluated in 67 patients with essential hypertension, and its therapeutic efficacy was compared with atenolol in a placebo run-in, single-blind, cross-over trial. Enalapril significantly reduced blood pressure in all grades of essential hypertension. As monotherapy it 'normalized' blood pressure in 88%, 50% and 25% of patients with mild, moderate and severe hypertension respectively. Optimal dose for most of the patients was 20 to 40 mg/day. Comparison with atenolol revealed almost parallel efficacy of the two drugs, although enalapril produced a significantly greater reduction in systolic blood pressure in patients with mild and moderate hypertension (P less than 0.01 in each group). No serious side effects were encountered with either drug. Enalapril, therefore, has a potent and slightly superior antihypertensive effect to that of atenolol, and may be used as a 'first-step' drug in the treatment of hypertensive patients.

Antihypertensive Effect of Enalapril in Essential Hypertension: Role of Prostacyclin

The effects of enalapril alone and in combination with the cyclooxygenase inhibitors sulindac and indomethacin on blood pressure (BP), plasma aldosterone, renin activity and converting enzyme activity were evaluated in 29 patients with mild to moderate essential hypertension, 26 of whom had low plasma renin activity. Patients were randomly assigned to one of three treatment groups. All patients underwent a 4-week placebo phase (phase I), then received enalapril (20 mg BID) for 4 weeks (phase II). In phase III, group I (n = 10) continued on enalapril alone; group II (n = 9) received sulindac 200 mg BID plus enalapril, and group III (n = 10) received indomethacin 50 mg BID plus enalapril, all for 4 weeks. Enalapril lowered BP significantly (mean supine BP 149/100 in phase I vs. 134/90 in phase II, p less than 0.05) without inhibiting aldosterone production. The BP effect was not blunted by concomitant administration of sulindac or indomethacin. Enalapril lowered converting enzyme activity to 25% to 30% of baseline and tended to increase renin activity. In the 10 patients who received indomethacin (group III), the effects of enalapril alone and enalapril plus indomethacin on urinary excretion of 6-keto prostaglandin F1 alpha (PGF1 alpha), a stable metabolite of prostacyclin (PGI2), were examined. Enalapril increased urinary 6-keto PGF1 alpha in group III from 118 +/- 23 to 194 +/- 38 ng/g creatinine (p less than 0.05), while addition of indomethacin reduced 6-keto PGF1 alpha to basal levels (138 +/- 26 ng/g creatinine).(ABSTRACT TRUNCATED AT 250 WORDS)

An Evaluation of the Pharmacodynamics and Pharmacokinetics of Nicardipine Combined with Enalapril in Essential Hypertension

Recent observations suggest that calcium antagonists may enhance the antihypertensive effects of angiotensin-converting enzyme (ACE) inhibitors. Twelve essential hypertensives who had blood pressures greater than 160/90 after a minimum of 6 weeks of monotherapy with the ACE inhibitor enalapril 20 mg daily received additional treatment with nicardipine 30 mg t.i.d. and placebo, each for 2 weeks, in a double-blind crossover study. The combination of nicardipine with enalapril was well tolerated. The addition of the first dose of nicardipine was associated with significant reductions (p less than 0.05) in blood pressure during the first 4 h: from a baseline of 165/99 to 128/80 (supine) at 2 h after nicardipine as compared with 167/101-146/90 following placebo. Two weeks of combined treatment with nicardipine and enalapril significantly reduced the predosing blood pressure, 12 h after the last dose of nicardipine (158/96 as compared with 172/106 with placebo), and there were further significant reductions in blood pressure during the subsequent dosage interval. The profile of plasma ACE inhibition and the pharmacokinetics of enalaprilat were unaffected by the addition of nicardipine. These results suggest that nicardipine and enalapril are an effective and well-tolerated antihypertensive combination.

Enalapril and the Kidney

Essential hypertension is characterized by increased renal vascular resistance, which also has definite implications for renal sodium handling. We studied the possibility of correcting these abnormalities by inhibiting angiotensin-converting enzyme with enalapril. Enalaprilic acid produced renal vasodilation. This, particularly postglomerular, vasodilation was accompanied with an increase in sodium excretion. The natriuresis was positively correlated to initial plasma renin activity. During continuous treatment with enalapril up to 12 weeks, this vasodilation persisted in 22 patients with essential hypertension. We also showed that orally administered enalapril induces natriuresis, both during a 50-mmol and during a 200-mmol sodium intake a day. This natriuresis caused a net negative sodium balance of approximately 120-140 mmol Na after 1 week of enalapril therapy. This was accompanied with a fall in body weight. We conclude that enalapril in essential hypertension alleviates the angiotensin-II-mediated abnormalities in renal hemodynamics and sodium excretion.

Natriuretic effect and changes in renal haemodynamics induced by enalapril in essential hypertension.

The purpose of this study was to evaluate the natriuretic effect and renal haemodynamic changes induced by enalapril in patients with essential hypertension. In a group of 11 patients with mild to moderate hypertension with normal renal function, and on a controlled sodium intake (80 mmol/day), a decrease in systolic and diastolic blood pressure was observed (p less than 0.001) after 16 weeks of enalapril treatment (20 mg/day), without a change in heart rate. An increase in plasma renin activity (p less than 0.05) without changes in serum aldosterone, and a decrease in exchangeable sodium (p less than 0.001) were present at the end of the treatment period. In 10 hypertensive patients also taking a dietary sodium of 80 mmol/day, the renal haemodynamics, humoral changes, and urinary sodium excretion were measured during 4 days of enalapril treatment (20 mg/day). There was an increase in urinary sodium excretion on the 3rd and 4th days of treatment (p less than 0.01). The effective renal plasma flow and fractional sodium excretion increased 72 hours after the beginning of treatment (p less than 0.01); the glomerular filtration rate did not change, and filtration fraction decreased at 72 hours. Mean blood pressure fell 2 hours after the first dose (p less than 0.01), and the maximum drop in intrarenal vascular resistance occurred after 72 hours of treatment (p less than 0.01). Plasma renin activity increased (p less than 0.05) and serum aldosterone decreased (p less than 0.01) 2 hours after the first dose. Thereafter, serum aldosterone increased progressively until it reached values similar to those with placebo at 48 and 72 hours of treatment. Urinary kallikrein fell during the 2nd and 3rd day of treatment (p less than 0.01). It was concluded that the decrease in exchangeable sodium was due to a natriuretic effect of enalapril. This effect presumably results from renal haemodynamic changes due to the reduction of angiotensin II. Other mechanisms, such as the reduction of aldosterone and accumulation of kinins, could be contributory factors.

Plasma enalapril levels and hormonal effects after short- and long-term administration in essential hypertension.

Enalapril lowers blood pressure both acutely and during long-term therapy in patients with essential hypertension. After a single 10 mg dose of enalapril a close relationship between plasma enalaprilic acid (MK-422) levels, angiotensin converting enzyme (ACE) inhibition and the acute hypotensive and hormonal effects was demonstrated. During long-term administration of enalapril, a similar relationship between the plasma enalaprilic acid level, ACE inhibition and the hypotensive effect was shown, although the dose-response curve for plasma enalaprilic acid to ACE inhibition was displaced to the right compared to the acute dose-response curve. Several weeks' administration of enalapril was needed to reach stable plateau levels of plasma enalaprilic acid and ACE inhibition. During long-term treatment with enalapril in essential hypertension, there was sustained inhibition of ACE and the associated hormonal changes.