Hemodynamic and antihypertensive effects of the new oral angiotensin-converting-enzyme inhibitor MK-421 (enalapril).

Publisher Website
Google Scholar
Abstract
The antihypertensive, hemodynamic, and humoral effects of the new converting enzyme inhibitor enalapril (MK-421) were assessed by sequential studies during 3 mo. of uninterrupted treatment (20 mg twice daily) in 10 hypertensive patients. Six achieved good blood pressure (mean arterial pressure) control with enalapril alone (from 126 .+-. 7.0 mm Hg pretreatment to 105 .+-. 1.6 mm Hg at 3 mo., P < 0.05). The other 4 required the addition of diuretics (hydrochlorothiazide 25 mg orally twice daily) at different stages of follow-up, with resultant blood pressure control (128 .+-. 9.6 mm Hg pretreatment to 113 .+-. 1.9 mm Hg at 2 mo. after the addition of diuretics). Neither the acute nor long-term blood pressure response could be predicted from the pretreatment levels of plasma renin activity. The blood pressure reduction during enalapril therapy was characterized by a decrease in total peripheral resistance (53 .+-. 2.5 U .cntdot. M2 pretreatment to 38 .+-. 3.0 U .cntdot. M2 at 3 mo., P < 0.05) with no significant change in cardiac output or heart rate. This lack of reflex tachycardia could not be ascribed to baroreceptor dysfunction since the response to head-up tilt (the increase in diastolic blood pressure, in heart rate and in plasma catecholamines) was normal and not significantly different from pretreatment response. Average blood volume did not change (91 .+-. 4.3% or normal in the pretreatment period to 93 .+-. 2.9% after 3 mo. of therapy, P = NS [not significant]) despite the significant lowering of arterial pressure with enalapril alone (n = 6). This could have been possibly related to the reduction in plasma aldosterone (12.6 .+-. 2.3 to 8 .+-. 0.9 ng/dl, P < 9.95) induced by treatment. In conclusion, the hemodynamic consequences of blood pressure reduction by enalaprol were similar to those produced by other converting-enzyme inhibitors and angiotensin II antagonists. The hemodynamic effects of enalapril apparently were related to interference with the generation of angiotensin II rather than a direct action of the drug.