Document Detail


Impaired 11-beta hydroxysteroid dehydrogenase type 2 activity in sweat gland ducts in human essential hypertension.
MedLine Citation:
PMID:  14981055     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Brigitte Bocchi; Sabine Kenouch; Maxime Lamarre-Cliche; Martine Muffat-Joly; Michel Hubert Capron; Jean Fiet; Gilles Morineau; Michel Azizi; Jean Pierre Bonvalet; Nicolette Farman
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2004-02-23
Journal Detail:
Title:  Hypertension     Volume:  43     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2004 Apr 
Date Detail:
Created Date:  2004-03-26     Completed Date:  2004-08-10     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  803-8     Citation Subset:  IM    
Affiliation:
INSERM U478, Faculté de Médecine X, Bichat, Université Paris 7, Paris, France.
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MeSH Terms
Descriptor/Qualifier:
11-beta-Hydroxysteroid Dehydrogenase Type 2 / genetics,  metabolism*
Adrenal Cortex Hormones / blood,  urine
Adult
Aldosterone / blood
Bicarbonates / blood
Biopsy
Blood Glucose / analysis
Body Mass Index
Chromatography, High Pressure Liquid
Corticosterone / metabolism
Creatinine / blood
Cross-Sectional Studies
Electrolytes / blood,  urine
Humans
Hypertension / blood,  enzymology*,  genetics,  urine
Male
Middle Aged
NAD / metabolism
Pilot Projects
Renin / blood
Sensitivity and Specificity
Sweat Glands / enzymology*
Uric Acid / blood
Chemical
Reg. No./Substance:
0/Adrenal Cortex Hormones; 0/Bicarbonates; 0/Blood Glucose; 0/Electrolytes; 50-22-6/Corticosterone; 52-39-1/Aldosterone; 53-84-9/NAD; 60-27-5/Creatinine; 69-93-2/Uric Acid; EC 1.1.1.146/11-beta-Hydroxysteroid Dehydrogenase Type 2; EC 3.4.23.15/Renin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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