Effect of dietary sodium on angiotensin-converting enzyme (ACE) inhibition and the acute hypotensive effect of enalapril (MK-421) in essential hypertension.
The hormonal and hypotensive effects of a single oral 10 mg dose of enalapril (MK-421), were assessed by a double-blind randomized trial in 12 subjects with essential hypertension, during a 100 and 40 mmol/day sodium intake. Peak serum MK-421 appeared 1 h following oral dosage. The bioactive conversion product of MK-421 (the parent diacid MK-422) appeared later, was maximal 4 h following dosage, and was still detectable 24 and 32 h later. Serum angiotensin-converting enzyme (ACE) activity was inhibited maximally at 4 h (by 57 +/- 4% of control activity) and had a similar time course to the serum MK-422 level. Plasma angiotensin II and aldosterone fell during ACE inhibition, but no change in bradykinin was detected. Reciprocal rises in plasma renin and angiotensin I occurred with a similar time course to ACE inhibition. Sodium depletion did not alter drug levels, basal serum ACE nor the time course of its inhibition. The initial blood pressure was however significantly lower when the subjects had been on the 40 mmol/day sodium diet. Blood pressure fell in all subjects and the fall was maximal 4-8 h following MK-421. There was a close correlation between plasma drug level, ACE inhibition and the hypotensive effect. These results suggest that regardless of the final mechanism for the antihypertensive action of MK-421 it is a consequence of its inhibition of ACE.
D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000097:blood; D000803:Angiotensin I / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors; D001920:Bradykinin / Q000097:blood; D002986:Clinical Trials as Topic; D004039:Diet, Sodium-Restricted; D004151:Dipeptides / Q000097:blood / Q000627:therapeutic use*; D004311:Double-Blind Method; D004656:Enalapril; D015773:Enalaprilat; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000178:diet therapy / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D011897:Random Allocation; D012083:Renin / Q000097:blood; D012964:Sodium / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D004151:Dipeptides; D000804:Angiotensin II; D000450:Aldosterone; D004656:Enalapril; D000803:Angiotensin I; D012964:Sodium; D007703:Peptidyl-Dipeptidase A; D012083:Renin; D015773:Enalaprilat; D001920:Bradykinin