Changes in the pathophysiologic profile of blood pressure determinants during short-term enalapril administration

To assess dose-related effects of enalapril, we treated eight 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, enalapril was given in single daily doses, starting with 1.25 mg and increasing dosage until blood pressure was adequately controlled. At 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 norepinephrine, renin, and aldosterone. With higher doses there was a more pronounced reduction in converting enzyme activity, whereas angiotensin II, aldosterone, and blood pressure all fell significantly. Renin levels rose, but norepinephrine and epinephrine were reduced. In a second study 20 hypertensive subjects were studied before and after 10 days of continued treatment with enalapril. Again, systolic and diastolic pressure were significantly reduced. Tachycardia or orthostatic hypotension did not occur. Endocrine changes were similar to those after a single effective dose of enalapril. In addition, we found renal vasodilation and enhanced natriuresis together with a 1.2 kg decrement in body weight. Concurrently, plasma volume rose but renal blood flow remained unchanged. The data indicate that enalapril 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.