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.