Humoral and renal effects of MK-421 (enalapril) in hypertensive subjects.
To assess the effect of MK-421 (enalapril) we treated six hospitalized hypertensive patients receiving constant sodium intake with incremental doses of this new angiotensin-converting enzyme blocking drug. After a few days of placebo treatment, MK-421 was given in single daily doses, starting with 1.25 mg and increasing until blood pressure was adequately controlled. On the lowest dose, converting enzyme activity was reduced by 50%, but angiotensin II and blood pressure did not change significantly. There were, however, significant increases in noradrenaline, renin, and aldosterone. With higher doses there was a more pronounced reduction in converting enzyme activity, while angiotensin II, aldosterone, and blood pressure all fell significantly. Renin levels rose, but noradrenaline and adrenaline were reduced. Orthostatic hypotension was not observed. With continued treatment, renal vasodilatation and enhanced natriuresis occurred together with a 1.2 kg decrement in body weight. Concurrently plasma volume rose, but renal blood flow remained unchanged. The data indicate that MK-421 effectively lowers blood pressure, and it does so by converting enzyme inhibition; sodium loss and a decrease in sympathetic activity are associated features. Since plasma volume increased despite enhanced natriuresis, the drug may act both at the arteriolar and at the venular level.
D000328:Adult; D000804:Angiotensin II / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000378:metabolism*; D004151:Dipeptides / Q000627:therapeutic use*; D004656:Enalapril; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007668:Kidney / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D012079:Renal Circulation / Q000187:drug effects; D012083:Renin / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002395:Catecholamines; D004151:Dipeptides; D000804:Angiotensin II; D004656:Enalapril; D012083:Renin