Adrenal desensitization following prolonged acth administration to normal subjects

The aim of this investigation was to determine whether the adrenal, having reached the refractory state with respect to aldosterone secretion as a result of prolonged ACTH exposure, would respond to the other major stimuli of the mineralocorticoid: angiotensin II and K. Twelve healthy male volunteers on a normal Na and K intake and ambulatory received ACTH (40 IU, i.m.) twice daily for 5 days followed by 2 days of angiotensin II (5-13ng/kg body wt/min for 60min) or oral K citrate (30 mEq/h × 3). A discordance in the aldosterone-stimulating and pressor responses of angiotensin II was unmasked with only the latter response being positive following ACTH-induced refractoriness. In contrast to angiotensin II, K could selectively enhance aldosterone secretion by overcoming the inhibition in secretion of the mineralocorticoid induced by prolonged ACTH exposure.