| 11beta-hydroxysteroid dehydrogenase in cultured human vascular cells. Possible role in the development of hypertension. | |
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MedLine Citation:
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PMID: 10334808 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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11beta-Hydroxysteroid dehydrogenases (11beta-HSD) interconvert cortisol, the physiological glucocorticoid, and its inactive metabolite cortisone in humans. The diminished dehydrogenase activity (cortisol to cortisone) has been demonstrated in patients with essential hypertension and in resistance vessels of genetically hypertensive rats. 11beta-Hydroxysteroid dehydrogenase type 2 (11beta-HSD2) catalyzes only 11beta-dehydrogenation. However, a functional relationship between diminished vascular 11beta-HSD2 activity and elevated blood pressure has been unclear. In this study we showed the expression and enzyme activity of 11beta-HSD2 and 11beta-HSD type 1 (which is mainly oxoreductase, converting cortisone to cortisol) in human vascular smooth muscle cells. Glucocorticoids and mineralocorticoids increase vascular tone by upregulating the receptors of pressor hormones such as angiotensin II. We found that physiological concentrations of cortisol-induced increase in angiotensin II binding were significantly enhanced by the inhibition of 11beta-HSD2 activity with an antisense DNA complementary to 11beta-HSD2 mRNA, and the enhancement was partially but significantly abolished by a selective aldosterone receptor antagonist. This may indicate that impaired 11beta-HSD2 activity in vascular wall results in increased vascular tone by the contribution of cortisol, which acts as a mineralocorticoid. In congenital 11beta-HSD deficiency and after administration of 11beta-HSD inhibitors, suppression of 11beta-HSD2 activity in the kidney has been believed to cause renal mineralocorticoid excess, resulting in sodium retention and hypertension. In the present study we provide evidence for a mechanism that could link impaired vascular 11beta-HSD2 activity, increased vascular tone, and elevated blood pressure without invoking renal sodium retention. |
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Authors:
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H Hatakeyama; S Inaba; I Miyamori |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Hypertension Volume: 33 ISSN: 0194-911X ISO Abbreviation: Hypertension Publication Date: 1999 May |
Date Detail:
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Created Date: 1999-06-07 Completed Date: 1999-06-07 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7906255 Medline TA: Hypertension Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1179-84 Citation Subset: IM |
Affiliation:
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Third Department of Internal Medicine, Fukui Medical University (Japan). |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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11-beta-Hydroxysteroid Dehydrogenases Angiotensin II / physiology Base Sequence Cells, Cultured Chromatography, Thin Layer Coronary Vessels Corticosterone* / metabolism DNA Primers Gene Expression Humans Hydrocortisone / analysis, physiology Hydroxysteroid Dehydrogenases / analysis, genetics, physiology* Hypertension / etiology*, physiopathology Molecular Sequence Data Muscle Tonus Muscle, Smooth, Vascular / cytology, enzymology RNA, Messenger / genetics Receptors, Angiotensin / physiology |
| Chemical | |
Reg. No./Substance:
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0/DNA Primers; 0/RNA, Messenger; 0/Receptors, Angiotensin; 11128-99-7/Angiotensin II; 50-22-6/Corticosterone; 50-23-7/Hydrocortisone; EC 1.1.-/Hydroxysteroid Dehydrogenases; EC 1.1.1.146/11-beta-Hydroxysteroid Dehydrogenases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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