Site of Stimulation of Aldosterone Biosynthesis by Angiotensin and Potassium

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 aldo-sterone pathway and a new method for measuring plasma deoxycorticosterone permitted the design of experiments to determine whether angiotensin and potassium stimu-late 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 con-version 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 re-sponded both to angiotensin and to potassium with sig-nificant 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 deoxy-corticosterone without simultaneously inducing large increases in plasma deoxycortisol. It is concluded that the aldosterone-stimnulating effects of angiotensin and potassium are, at least in part, consequences of stimula-tion of the biosynthetic pathway at some point before the formation of deoxycorticosterone so as to increase the availability of aldosterone precursors