Regulation of aldosterone biosynthesis during sodium deficiency. Evidence for an essential role of the pituitary gland.
The aldosterone response to adrenocorticotropic hormone (ACTH) and angiotensin II (AII) was evaluated in patients with pituitary insufficiency before and after dietary sodium restriction (10 mEq Na+/day for 12 days). On normal sodium intake, plasma aldosterone concentration and plasma cortisol concentration failed to change from control levels in response to a single injection of ACTH or to a continuous 1-hour infusion of AII in patients with pituitary insufficiency. In response to dietary sodium restriction for 12 days, plasma renin activity (PRA) increased fivefold in patients with pituitary insufficiency, while plasma aldosterone concentration failed to increase significantly, averaging 11.0 +/- 3.1 before and 12.3 +/- 3.7 ng/dl (ns, p greater than 0.05) after sodium deficiency. Although aldosterone secretion failed to increase during sodium deficiency, the patients came into balance at 10 mEq without a significant change in arterial blood pressure (BP). In sharp contrast to the lack of aldosterone response to ACTH before sodium deficiency, plasma aldosterone concentration increased markedly from 12.9 +/- 3.3 to 156 +/- 17.3 ng/dl (p less than 0.001) in response to ACTH after sodium deficiency. Although the adrenal glomerulosa cells were markedly sensitive to ACTH during sodium deficiency, they remained almost totally refractory to AII since aldosterone secretion failed to increase significantly in response to continuous infusion of a pressor dose of AII for 1 hour. Replacement therapy with ACTH gel for 3 months in patients with pituitary insufficiency failed to restore a normal aldosterone response to either ACTH or AII. These data demonstrate that some non-ACTH pituitary factor(s) is essential for a normal aldosterone response to ACTH, AII, and sodium deficiency.
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000450:Aldosterone / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism*; D000804:Angiotensin II / Q000494:pharmacology; D001794:Blood Pressure; D004039:Diet, Sodium-Restricted; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D010900:Pituitary Diseases / Q000503:physiopathology; D010902:Pituitary Gland / Q000503:physiopathology*; D012083:Renin / Q000097:blood; D012964:Sodium / Q000172:deficiency* / Q000652:urine
D000804:Angiotensin II; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D012964:Sodium; D012083:Renin; D006854:Hydrocortisone