Inhibition of furosemide-induced kaliuresis in the rat by trilostane, an inhibitor of adrenal steroidogenesis.
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.
D015096:3-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors; D000315:Adrenalectomy; D000450:Aldosterone / Q000097:blood*; D000818:Animals; D013196:Dihydrotestosterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D004231:Diuresis / Q000187:drug effects; D005665:Furosemide / Q000494:pharmacology*; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D011188:Potassium / Q000652:urine*; D051381:Rats; D011919:Rats, Inbred Strains; D013148:Spironolactone / Q000494:pharmacology
D013196:Dihydrotestosterone; D013148:Spironolactone; D000450:Aldosterone; D005665:Furosemide; D015096:3-Hydroxysteroid Dehydrogenases; C009954:trilostane; D011188:Potassium