The
enzyme 11-beta
hydroxysteroid dehydrogenase type 2 plays a major role in blood pressure regulation. It metabolizes
glucocorticoid hormones into derivatives with low affinity for the
mineralocorticoid receptor, preventing its permanent occupancy by circulating
cortisol, which is 100- to 1000-fold more abundant than
aldosterone in the plasma. Inactivating mutations of the
enzyme result in severe
hypertension, as seen in children with
apparent mineralocorticoid excess syndrome. In patients with
essential hypertension, however, attempts to evidence
enzyme deficiency have been inconclusive. In this pilot study, its catalytic activity was measured directly in
aldosterone-sensitive sweat gland ducts collected from skin biopsy samples of 10 male normotensive subjects and 10 subjects with
essential hypertension (more than 140 to 90 mm Hg) with no sign of hypermineralocorticism. Isolated ducts were assayed for
nicotinamide-dinucleotide-dependent
dehydrogenase activity (transformation of tritiated
corticosterone into tritiated-11 dehydrocorticosterone, as measured by high-pressure liquid chromatography). Hypertensive patients exhibited significantly lower 11-beta
hydroxysteroid dehydrogenase type 2 activity (9.7+/-4.7 femtomoles per 3 mm length of duct and per 10 minutes incubation, median+/-SD) than did normotensive subjects (15.9+/-2.6). Such defect was undetectable using the classical urinary
corticosteroid metabolism indexes, probably because of compensatory mechanisms. Relations between these findings and blood pressure levels should benefit from direct
enzyme measurements in the vasculature. In conclusion, this cross-sectional study points to partial 11-beta
hydroxysteroid dehydrogenase type 2 deficiency as a novel feature of
essential hypertension, which should stimulate search for new signaling pathways and therapeutical targets.