11-Dehydrocorticosterone in the presence of carbenoxolone is a more potent sodium retainer than corticosterone.
In vivo, corticosterone and 11-dehydrocorticosterone are interconverted in the liver and possibly kidney by 11 beta-hydroxysteroid dehydrogenase. In an effort to evaluate the relevance of this reversible reaction in relation to urinary sodium and potassium excretion, we investigated the effects of 11-dehydrocorticosterone in the presence and absence of carbenoxolone, a potent inhibitor of the oxidative component of 11 beta-hydroxysteroid dehydrogenase, and compared them with the effects of similar doses of corticosterone in carbenoxolone-treated rats. All experiments were performed on adrenalectomized male rats. Here we describe that in carbenoxolone-treated rats 11-dehydrocorticosterone and corticosterone display antinatriuretic activity, although under the conditions of this study 11-dehydrocorticosterone is a more potent sodium retainer than its parent steroid corticosterone. In addition, the antinatriuretic effects of 11-dehydrocorticosterone (like the antinatriuretic effects of corticosterone in carbenoxolone-treated rats) were blocked by the specific antimineralocorticoid RU28318.
Souness
G W
GW
Department of Pathology and Laboratory Medicine, Miriam Hospital, Providence, Rhode Island 02906.
Morris
D J
DJ
D000315:Adrenalectomy; D000818:Animals; D002229:Carbenoxolone / Q000494:pharmacology*; D003345:Corticosterone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D003404:Creatinine / Q000652:urine; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D009318:Natriuresis / Q000187:drug effects*; D011188:Potassium / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000494:pharmacology
D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; C041006:RU 28318; D003404:Creatinine; C003552:11-dehydrocorticosterone; D002229:Carbenoxolone; D011188:Potassium; D003345:Corticosterone