The 11 beta-OHSD inhibitor, carbenoxolone, enhances Na retention by aldosterone and 11-deoxycorticosterone.
Carbenoxolone sodium, CS, a liquorice derivative associated with hypertension and sodium retention, has been demonstrated to inhibit 11 beta-hydroxysteroid dehydrogenase, an enzyme that metabolizes cortisol and corticosterone to their respective inactive 11-dehydro products (cortisone and 11-dehydrocorticosterone). It has been proposed that the increased bioavailability of unmetabolized corticosterone and cortisol following 11 beta-OHSD inhibition allows these steroids to act on renal mineralocorticoid receptors to elicit the mineralocorticoid action. Here we describe how CS amplifies the antinatriuretic activity of aldosterone and deoxycorticosterone; the latter steroid is of particular importance in that it does not possess a hydroxyl group at the C-11 position in the steroid ring, indicating that another mechanism(s) in addition to 11 beta-OHSD inhibition is responsible for the amplification of the action of deoxycorticosterone.
Morris
D J
DJ
Department of Pathology and Laboratory Medicine, Miriam Hospital, Providence, Rhode Island.
Souness
G W
GW
D042842:11-beta-Hydroxysteroid Dehydrogenases; D015065:17-Hydroxycorticosteroids / Q000494:pharmacology*; D000315:Adrenalectomy; D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D002229:Carbenoxolone / Q000494:pharmacology*; D003350:Cortodoxone / Q000494:pharmacology*; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives*; D006913:Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism*
D015065:17-Hydroxycorticosteroids; D000450:Aldosterone; D012964:Sodium; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D002229:Carbenoxolone; D006034:Glycyrrhetinic Acid; D003350:Cortodoxone