Role of glucocorticoid in the development of glycyrrhizin-induced hypertension.
Role of alterations of corticosterone metabolism in the expression of the mineralocorticoid activity of glycyrrhizin was explored in rats. While the mineralocorticoid actions of oral glycyrrhizin were not observed in bilaterally adrenalectomized rats and dexamethasone treated rats, the mineralocorticoid actions of glycyrrhizin were fully expressed in bilaterally adrenalectomized rats supplemented with physiological doses of corticosterone. Similar mineralocorticoid actions were observed in rats given glycyrrhizin, deoxycorticosterone and pharmacological doses of corticosterone. Although increases in mean blood pressure were suppressed only by concurrent administration of spironolactone to glycyrrhizin- and deoxycorticosterone-treated rats, increases in mean blood pressure were attenuated by both the glucocorticoid antagonist RU 38486 and spironolactone in pharmacological doses of corticosterone administered rats. Pressor responses to norepinephrine and angiotensin II infusions in rats given deoxycorticosterone and pharmacological doses of corticosterone were significantly higher than in glycyrrhizin-treated rats. These results confirmed the functional significance of 11-beta-hydroxysteroid dehydrogenase in expression of the mineralocorticoid activity of glycyrrhizin.
Department of Internal Medicine, Tochigi National Hospital, Utsunomiya, Japan.
Y
Y
Kageyama
H
H
Suzuki
T
T
Saruta
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000311:Adrenal Glands / Q000502:physiology; D000315:Adrenalectomy; D000450:Aldosterone / Q000097:blood; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003345:Corticosterone / Q000494:pharmacology; D003900:Desoxycorticosterone / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000378:metabolism*; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000633:toxicity; D019695:Glycyrrhizic Acid; D006913:Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors; D006973:Hypertension / Q000139:chemically induced / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D008901:Mineralocorticoids / Q000378:metabolism; D011188:Potassium / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D012083:Renin / Q000097:blood; D013148:Spironolactone / Q000494:pharmacology
D005938:Glucocorticoids; D008901:Mineralocorticoids; D013148:Spironolactone; D003900:Desoxycorticosterone; D000450:Aldosterone; D019695:Glycyrrhizic Acid; D003907:Dexamethasone; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D012083:Renin; D006034:Glycyrrhetinic Acid; D011188:Potassium; D003345:Corticosterone