Hemodynamic and antihypertensive effects of the new oral angiotensin-converting-enzyme inhibitor MK-421 (enalapril).
The antihypertensive, hemodynamic, and humoral effects of the new converting-enzyme 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 less than 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 X M2 pretreatment to 38 +/- 3.0 U X M2 at 3 months, p less than 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).(ABSTRACT TRUNCATED AT 250 WORDS)
D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D001810:Blood Volume / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004151:Dipeptides / Q000494:pharmacology / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004656:Enalapril; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006852:Hydrochlorothiazide / Q000627:therapeutic use; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D004151:Dipeptides; D006852:Hydrochlorothiazide; D004656:Enalapril