Inhibition of furosemide-induced kaliuresis in the rat by trilostane, an inhibitor of adrenal steroidogenesis

• Published in: Proceedings of the Society for Experimental Biology and Medicine Vol. 177; no. 3; p. 388
• Main Authors: Harding, H R, Creange, J E, Potts, G O, Schane, H P
• Format: Journal Article
• Language: English
• Published: United States 01-12-1984
• Subjects: 3-Hydroxysteroid Dehydrogenases - antagonists & inhibitors; Adrenalectomy; Aldosterone - blood; Animals; Dihydrotestosterone - analogs & derivatives; Dihydrotestosterone - pharmacology; Diuresis - drug effects; Furosemide - pharmacology; Male; Natriuresis - drug effects; Potassium - urine; Rats; Rats, Inbred Strains; Spironolactone - pharmacology
• ISSN: 0037-9727
• DOI: 10.3181/00379727-177-41961

In rats treated with furosemide, urinary losses of water, sodium and potassium were accompanied by increased circulating levels of aldosterone. Trilostane, an inhibitor of adrenal 3 beta-hydroxysteroid dehydrogenase activity, prevented furosemide-induced hyperaldosteronism which resulted in a partial inhibition of diuretic-induced kaliuresis without a change in sodium and water excretion. Spironolactone, an antagonist of mineralocorticoid action with inherent diuretic activity, produced qualitatively similar effects to those of trilostane on urinary electrolyte excretion in furosemide-treated intact rats. However, mineralocorticoid-induced potassium loss in adrenalectomized rats was not altered by trilostane but was prevented by spironolactone reflecting the direct effect of spironolactone on the kidney. In addition, furosemide-induced kaliuresis in adrenalectomized rats was not prevented by trilostane. Therefore, although both trilostane and spironolactone reduce diuretic-induced potassium loss, spironolactone acts by competing with aldosterone for the mineralocorticoid receptor while trilostane appears to act exclusively by preventing secondary hyperaldosteronism.