The effect of chronic low-dose infusion of ACTH (1-24) on renin, renin-substrate, aldosterone and other corticosteroids in sodium replete and deplete man.

Abstract

Abstract. Low-dose infusions of ACTH 1-24 (5 U/day) of 4 days duration were performed in 2 healthy young men on a normal sodium diet and in 2 on a low sodium diet, in order to study the mechanism of the transient effect of ACTH on aldosterone secretion described by other authors using larger doses of ACTH. Cortisol secretion was continuously stimulated by ACTH. Plasma aldosterone (P-Al) and its urinary metabolites increased during the first two days of infusion and returned to control or below control levels subsequently. Plasma renin activity (PRA) was also transiently stimulated by ACTH. Changes in PRA were not caused by changes in plasma renin substrate concentration. The correlation between PRA and P-Al (r = + 0.78; n = 52) was highly significant (P < 0.01). Plasma levels of deoxycorticosterone (DOC), 18-OH-DOC and corticosterone were also transiently stimulated in subjects on a normal sodium diet, while the stimulation was better maintained in those on a low sodium diet. The results suggest that the transient effect of low-dose ACTH infusion on aldosterone secretion may in part be mediated by changes in the renin-angiotensin-system. Changes in plasma levels of angiotensin II, which controls early and late steps in the mineralocorticoid biosynthetic pathway, may determine the extent to which chronically elevated ATCH levels stimulate the release of aldosterone and, perhaps, even the release of DOC and corticosterone. On the normal sodium diet, sodium retention and a slight fall in serum potassium levels towards the end of ACTH infusion may have contributed to the depression of aldosterone release.