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

The antihypertensive, hemodynamic, and humoral effects of the new convertingenzyme inhibitor enalapril (MK-421) were assessed by sequential studies during 3 months 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 months, p < 0.05). The other four 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 months 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-M² pretreatment to 38 ± 3.0 U-M2 at 3 months, p < 0.05) with no significant change in cardiac output or heart rate. This lack of reflex tachycardia could not be ascribed to baroceptor 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% of normal in the pretreatment period to 93% ± 2.9% after 3 months of therapy, p = NS) 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 enalapril were similar to those produced by other converting-enzyme inhibitors and angiotensin II antagonists. These findings suggest that the hemodynamic effects of enalapril were related to interference with the generation of angiotensin II rather than a direct action of the drug.