Central hypertensinogenic effects of glycyrrhizic acid and carbenoxolone.
The apparent mineralocorticoid excess syndrome of patients ingesting large amounts of licorice or its derivatives is thought to be caused by the antagonism by these compounds of the enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD). 11 beta-HSD inactivates cortisol and corticosterone, allowing the more abundantly produced glucocorticoids access to the mineralocorticoid receptor (MR) in the kidney, where they act as mineralocorticoids. We have found that the infusion of both glycyrrhizic acid, an active principle of licorice, and carbenoxolone, a synthetic analogue, into a lateral ventricle of the brain [intracerebroventricular (icv)] of a rat, at a dose less than that which has an effect when infused subcutaneously, produces hypertension. Furthermore, the hypertension produced by the oral administration of carbenoxolone or glycyrrhizic acid is blocked by the icv administration of RU 28318, an MR antagonist, at a dose below that which has an effect on blood pressure when infused subcutaneously. While the oral administration caused saline polydipsia and polyuria typical of chronic systemic mineralocorticoid excess, the icv licorice derivatives produced hypertension without affecting saline appetite. Sensitizing the rats to mineralocorticoid hypertension by renal mass reduction and increasing salt consumption was not necessary for the production of hypertension. These findings provide additional evidence for a central role in blood pressure control by mineralocorticoids that is distinct from their renal effects. They also suggest that more is involved in licorice-induced hypertension than only inhibition of 11 beta-HSD.
Gomez-Sanchez
E P
EP
Research Service, James A. Haley Veterans Hospital, Tampa, Florida.
Gomez-Sanchez
C E
CE
D000284:Administration, Oral; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000502:physiology*; D002229:Carbenoxolone / Q000494:pharmacology; D003345:Corticosterone / Q000494:pharmacology; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D019695:Glycyrrhizic Acid; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology; D007276:Injections, Intraventricular; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013148:Spironolactone / Q000031:analogs & derivatives / Q000494:pharmacology
D013148:Spironolactone; D019695:Glycyrrhizic Acid; C041006:RU 28318; D002229:Carbenoxolone; D006034:Glycyrrhetinic Acid; D003345:Corticosterone