Site of stimulation of aldosterone biosynthesis by angiotensin and potassium

Abstract

Studies were undertaken to determine what part of the aldosterone biosynthetic pathway is stimulated by angiotensin and potassium. The availability of a method for isolating the early portion of the aldosterone pathway and a new method for measuring plasma deoxycorticosterone permitted the design of experiments to determine whether angiotensin and potassium stimulate the pathway before deoxycorticosterone. To eliminate ACTH-dependent steroid synthesis, the experiments were performed in subjects receiving constant dosage of dexamethasone. To minimize the intra-adrenal conversion of deoxycorticosterone to corticosterone, all subjects also received constant dosage of metyrapone. Plasma deoxycortisol was measured as an index of the activity of the zona fasciculata. In the absence of changes in plasma deoxycortisol, one may infer that changes in plasma deoxycorticosterone represent changes in function of zona glomerulosa, the site of aldosterone formation. Under these conditions, human subjects responded both to angiotensin and to potassium with significant increases in plasma deoxycorticosterone but without significant increases in plasma deoxycortisol. In contrast, small doses of ACTH given under similar conditions never induced increases in plasma deoxycorticosterone without simultaneously inducing large increases in plasma deoxycortisol. It is concluded that the aldosterone-stimulating effects of angiotensin and potassium are, at least in part, consequences of stimulation of the biosynthetic pathway at some point before the formation of deoxycorticosterone so as to increase the availability of aldosterone precursors.