This Article Full Text Full Text (PDF) All Versions of this Article: 43/4/803    most recent 01.HYP.0000121362.64182.adv1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bocchi, B. Articles by Farman, N. Search for Related Content PubMed PubMed Citation Articles by Bocchi, B. Articles by Farman, N. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Medline Plus Health Information High Blood Pressure Related Collections ACE/Angiotension receptors Cell signalling/signal transduction Hypertension - basic studies Ion channels/membrane transport Clinical Studies Other etiology

(Hypertension. 2004;43:803.)
© 2004 American Heart Association, Inc.

Scientific Contributions

Impaired 11-ß Hydroxysteroid Dehydrogenase Type 2 Activity in Sweat Gland Ducts in Human Essential Hypertension

Brigitte Bocchi; Sabine Kenouch; Maxime Lamarre-Cliche; Martine Muffat-Joly; Michel Hubert Capron; Jean Fiet; Gilles Morineau; Michel Azizi; Jean Pierre Bonvalet; Nicolette Farman

From INSERM U 478 (B.B., S.K., J.P.B., N.F.) and IFR 02 (M.M.-J.), Faculté de Médecine X, Bichat, Université Paris 7; Centre d’Investigation Clinique 9201 AP-HP/Inserm (M.L.-C., M.A.), Hôpital Européen Georges Pompidou; Fondation Searle France (M.H.C.); and Laboratoire de Biologie Hormonale (J.F., G.M.), Hôpital Saint Louis, Paris, France.

Correspondence to N. Farman, INSERM U478, Faculté de Médecine X, Bichat, BP 416, 75870 Paris Cedex 18, France. E-mail farman{at}bichat.inserm.fr

The enzyme 11-ß 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-ß 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-ß hydroxysteroid dehydrogenase type 2 deficiency as a novel feature of essential hypertension, which should stimulate search for new signaling pathways and therapeutical targets.

Key Words: mineralocorticoids • aldosterone • corticosterone • hypertension • clinical trials

This article has been cited by other articles:

				Y. Liu, D. Mladinov, J. L. Pietrusz, K. Usa, and M. Liang Glucocorticoid response elements and 11{beta}-hydroxysteroid dehydrogenases in the regulation of endothelial nitric oxide synthase expression Cardiovasc Res, January 1, 2009; 81(1): 140 - 147. [Abstract] [Full Text] [PDF]