Effect of Angiotensin II on Adrenal and Pituitary Function in Man1

The acute effect of angiotensin II on plasma cortisol, aldosterone and immunoassayable ACTH (I-ACTH) was studied in normal subjects and in 3 patients with hypopituitarism. Angiotensin II, in a pressor dose given by constant infusion for 1 hr, increased plasma aldosterone to 28.5 ±5 (sd) ng/100 ml, while ACTH had a significantly greater effect, increasing aldosterone to 64 ±10 mean ±(sd) ng/100 ml. ACTH (0.1 μg/kg/hr, βl–24) increased cortisol 3- to 4- fold; however, angiotensin II in a subpressor dose did not increase cortisol. A pressor dose of angiotensin significantly increased I-ACTH from 27.8 ±8.8 (sd) to 60.4 ±20 (sd) pg/ml (p<0.01). A rise was noted in every angiotensin infusion despite an apparent fall in cortisol whether administered in the morning or afternoon. In contrast, a subpressor infusion (1/3 pressor dose), or a pressor infusion of angiotensin after an overnight dexamethasone dose (1 mg q 12 hr), did not increase the plasma I-ACTH. In 3 patients with pituitary insufficiency, who responded to ACTH but not to metyrapone, a constant infusion of ACTH (20 ng/kg/min, β1–24) increased the plasma cortisol, but, when pressor angiotensin was also given, a fall in plasma cortisol was noted. When I-ACTH was suppressed in normal subjects for 12 hr with 1 mg dexamethasone, pressor angiotensin II resulted in only a minimal increase in plasma aldosterone (14 ±4 ng/100 ml). These studies indicate that there is a relationship in man between the renin-angiotensin and pituitary ACTH systems. Angiotensin II appears to increase ACTH by altering cortisol production in man. In order to obtain a complete in vivo response to angiotensin II, a normal dynamic relationship between adrenal cortisol and pituitary ACTH is required.