5 alpha-Dihydro-11-deoxycorticosterone as a mineralocorticoid agonist and antagonist: evidence for a weak mineralocorticoid as an antagonist of potent mineralocorticoids.
To evaluate the possibility that 5 alpha-dihydro-11-deoxycorticosterone (5 alpha-DH-DOC), a weak mineralocorticoid, is an antagonist of a more potent mineralocorticoid, aldosterone, 0.25 microgram aldosterone was injected into adrenalectomized rats simultaneously with 200-800 micrograms 5 alpha-DH-DOC and urinary Na/K ratio and Na and K excretion were evaluated. Urinary Na/K ratio and Na excretion were significantly lower than those of control rats regardless of whether rats were treated with 0.25 microgram aldosterone alone or 400-800 micrograms 5 alpha-DH-DOC alone. Urinary Na/K ratio and Na excretion of rats given a combination of 0.25 microgram aldosterone plus 400-800 micrograms 5 alpha-DH-DOC were significantly higher than those of rats given 0.25 microgram aldosterone alone. None of the treatment caused significant changes in urinary K excretion. The results demonstrate that 5 alpha-DH-DOC, a weak mineralocorticoid, is an antagonist of the sodium-retaining action of a more potent mineralocorticoid, aldosterone. Progesterone which has weak mineralocorticoid activity is also known as an antagonist of more potent mineralocorticoids. The results of the present study demonstrate further evidence that weak mineralocorticoids may work as antagonists of more potent mineralocorticoids.
Third Department of Internal Medicine, University of Tokyo Faculty of Medicine, Japan.
H
H
Sekihara
Y
Y
Yazaki
D000450:Aldosterone / Q000494:pharmacology; D000818:Animals; D003900:Desoxycorticosterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists; D008901:Mineralocorticoids / Q000494:pharmacology*; D011188:Potassium / Q000652:urine*; D011277:Pregnanediones; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000652:urine*
D000451:Mineralocorticoid Receptor Antagonists; D008901:Mineralocorticoids; D011277:Pregnanediones; D003900:Desoxycorticosterone; D000450:Aldosterone; D012964:Sodium; C084598:hydroxydione; D011188:Potassium