AJP - Endocrinology and Metabolism, Vol 263, Issue 6 E1125-E1130, Copyright © 1992 by American Physiological Society
Central hypertensinogenic effects of glycyrrhizic acid and carbenoxolone
E. P. Gomez-Sanchez and C. E. Gomez-Sanchez
Research Service, James A. Haley Veterans Hospital, Tampa, Florida.
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.
