SUMMARY The orally active angiotensin converting enzyme inhibitor, captopril, was administered to 23 hypertensive patients maintained for 10 days on a constant sodium and potassium intake. Because the antihypertensive action of the drug might depend in part oo a functional reduction in angiotensin II levels, we sought to determine whether continuous blockade of the renln axis might be reflected in induced changes in aldosterone secretion and by consequent changes in sodium and potassium balance. Blood pressure fell in response to captopril in 22 of the 23 patients studied, reaching a nadir after 7 to 10 days of continued treatment. Captopril promptly produced falls in urinary aldosterone excretion and plasma aldosterone in all patients except one with low plasma renln activity. Moreover, aldosterone secretion remained suppressed in the face of progressive potassium retention and increased plasma potassium, effects that normally increase aldosterone secretion. Concurrently, the drug produced negative sodium balance in most patients, although four patients (three of whom had renal artery stenosis) developed significant sodium retention when blood pressure was reduced.
These effects on aldosterone secretion and potassium balance, as well as the concurrent drug-induced reductions in blood pressure, were greatest in patients with high plasma renln activity and least in the low-renin patients. After 7 days of maintenance treatment, the changes in mean arterial pressure were also directly related to changes in aldosterone excretion (r = 0.73, p < 0.001) and inversely related to changes in serum potassium concentration (r = −0.72, p < 0.001).
Altogether, the observed effects on aldosterone and electrolyte balance strongly suggest that inhibition of angiotensin converting enzyme in vivo produces a sustained reduction in biologically active angiotensin II levels. These findings, together with previous evidence that the antihypertensive action of the drug is also related to the pretreatment plasma renln level, make it reasonable to suspect that reductions in blood pressure during captopril treatment result in some large measure from blockade of angiotensin II formation.