Acute effects of digoxin on plasma aldosterone and cortisol in monkeys

Digoxin, a cardiac glycoside, is used to increase cardiac contractility via inhibition of Na⁺/K⁺-adenosinetriphosphatase (ATPase) and increase intracellular calcium in congestive heart failure. Inhibitory effects of digoxin have been demonstrated on the biosynthesis of gonadal hormones and adrenal glucocorticoids in rats. However, acute effects of digoxin on levels of adrenal corticosteroid hormones in the primates in vivo are uncertain. Therefore, we test the hypothesis that a single injection of digoxin decreases the secretion of aldosterone and cortisol in monkeys. An intravenous injection of digoxin (1 μg/kg) inhibited basal and adrenocorticotropin (ACTH)- or KCl-stimulated aldosterone release in monkeys. Furthermore, digoxin induced a decrease in ACTH- and KCl-stimulated cortisol release. Administration of digoxin did not alter plasma concentrations of Na⁺ and K⁺. Ouabain, a selective inhibitor of Na⁺/K⁺-ATPase, did not affect ACTH- or KCl-stimulated aldosterone and cortisol release. These results revealed that injection of digoxin induced an inhibitory effect on aldosterone and cortisol secretion in monkeys. Because ouabain did not affect levels of plasma aldosterone or cortisol, we suggest that (1) the Na⁺/K⁺-ATPase pathway may not be involved in the mechanism of action of digoxin on aldosterone or cortisol secretion in monkeys and/or (2) the Na⁺/K⁺-ATPase is more sensitive to digoxin than to ouabain in monkeys.