Time Course and Effect of Sodium Intake on Vascular and Hormonal Responses to Enalapril (MK 421) in Normal Subjects

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Abstract
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 less than 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 (AII) 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 less than 0.01) and AII decrements (p less than 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 AII occurred at any dose of enalapril; however, PRA increased modestly but significantly (p less than 0.01) after administration of 5, 10, and 20 mg enalapril. Plasma aldosterone declined modestly but significantly, 2 (p less than 0.05) and 4 (p less than 0.01) h after the 10 mg dose.(ABSTRACT TRUNCATED AT 250 WORDS)

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