ENDOGENOUS INHIBITORS OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE IN HYPERTENSION

Exogenous inhibitors of 11 beta-hydroxysteroid dehydrogenase (e.g. gly cyrrhetinic acid, a constituent of licorice) raise blood pressure by a llowing cortisol to activate mineralocorticoid receptors. Endogenous 1 1 beta-dehydrogenase inhibitors, called glycyrrhetinic acid-like facto rs (GALFs), have been extracted from urine. Increased GALFs could expl ain the impairment of 11 beta-dehydrogenase in essential hypertension and ectopic ACTH syndrome. We extracted urine on Sep-Paks and quantifi ed GALFs by their inhibition of 11 beta-dehydrogenase bioactivity in m icrosomes from rat liver. GALFs have no diurnal rhythm and were no dif ferent after dexamethasone treatment, in patients with low ACTH, or in 4 patients with ectopic ACTH secretion. In 79 subjects, GALF excretio n did not correlate with blood pressure. In 17 subjects, GALF excretio n did not correlate with indices of mineralocorticoid receptor activat ion or 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-dehydrogenas e activity, GALFs are unlikely to play a pathophysiological role.