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Enalapril (MK 421) is a long-acting angiotensin converting-enzyme inhibitor which specifically lacks the sulfhydryl group of captopril. We measured arterial pressure and hormonal responses that occurred in 22 normotensive subjects treated with increasing doses of enalapril (2.5, 5, 10, and 20 mg) once daily, who were on either low (10 mEq) or high (200 mEq) sodium diets. In sodium-restricted subjects (n = 12), mean diastolic blood pressure declined from control levels in a dose-related fashion during the first 2 h. The mean 24-h diastolic blood pressure values were significantly lower than control (p < 0.01) at all doses, with the greatest declines occurring with the 10 and 20 mg doses. Accompanying the decline in blood pressure was a significant increase in plasma renin activity (PRA) and reduction in plasma angiotensin II (All) and aldosterone levels. As with blood pressure, the greatest changes were observed with the 5, 10, and 20 mg doses. However, only the 20 mg dose of enalapril produced prolonged and significant PRA increments (p < 0.01) and All decrements (p < 0.05) of at least 24 h in duration. In sodium-replete subjects (n = 10), a similar pattern of diastolic blood pressure responses was observed; however, the effect of the drug was not so profound. No significant decrease in All occurred at any dose of enalapril; however, PRA increased modestly but significantly (p < 0.01) after administration of 5, 10, and 20 mg enalapril. Plasma aldosterone declined modestly but significantly, 2 (p < 0.05) and 4 (p < 0.01) h after the 10 mg dose. While enalapril lowered blood pressure in a dose-response fashion in subjects on both low and high sodium diets, its effects were more dramatic in sodium-restricted subjects. Plasma norepinephrine, epinephrine, bradykinin, and prostaglandin E2 metabolite levels, however, were unchanged during enalapril treatment, with either sodium intake. Thus, the mechanism for the hypotensive response in sodium-loaded subjects is unclear, as there were no changes in any of the vasoactive hormones measured. These data suggest a potentially more specific mechanism of action for enalapril in inhibiting the renin-angiotensin system in sodium-restricted subjects compared with captopril or teprotide, but they do not explain the significant blood pressure reduction in sodium-loaded subjects which was unrelated to detectable changes in circulating All. Possibly, changes in bradykinin degradation, prostaglandin production, or All formation at the local tissue level, which may not be reflected by changes in circulating hormone concentrations, may explain this discrepancy.
Shoback et al. (Tue,) studied this question.