Endogenous inhibitors of 11 beta-hydroxysteroid dehydrogenase in hypertension

Abstract

Exogenous inhibitors of 11 beta-hydroxysteroid dehydrogenase (e.g. glycyrrhetinic acid, a constituent of licorice) raise blood pressure by allowing cortisol to activate mineralocorticoid receptors. Endogenous 11 beta-dehydrogenase inhibitors called glycyrrhetinic acid-like factors (GALFs), have been extracted from urine. Increased GALFs could explain the impairment of 11 beta-dehydrogenase in essential hypertension and ectopic ACTH syndrome. We extracted urine on Sep-Paks and quantified GALFs by their inhibition of 11 beta-dehydrogenase bioactivity in microsomes from rat liver. GALFs have no diurnal rhythm and were no different after dexamethasone treatment, in patients with low ACTH, on in 4 patients with ectopic ACTH secretion. In 79 subjects, GALF excretion did not correlate with blood pressure. In 17 subjects, GALF excretion did not correlate with indices of mineralocorticoid receptor activation on 11 beta-dehydrogenase activity. We conclude that GALFs are not ACTH dependent and have no measurable effect on 11 beta-dehydrogenase in vivo. In hypertension associated with impaired 11 beta-dehydrogenase activity GALFs are unlikely to play a pathophysiological role.