| 11beta-hydroxysteroid dehydrogenase in human vascular cells. | |
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MedLine Citation:
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PMID: 10760066 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Aldosterone selectivity in mineralocorticoid target tissues is mainly due to 11beta-hydroxysteroid dehydrogenase (11betaHSD), which converts cortisol to its inactive metabolite cortisone in humans. The defect of dehydrogenase activity would thus allow type 1 mineralocorticoid receptor (MR) to be occupied mostly by cortisol. It has been postulated that 11betaHSD type 2 (11betaHSD2) plays a significant role in conferring ligand specificity on the MR. We have demonstrated the diminished dehydrogenase activity in resistance vessels of genetically hypertensive rats. However, the mechanism that could link impaired vascular 11betaHSD activity and elevated blood pressure has been unclear. In this study, we showed the enzyme activity in human coronary artery smooth muscle cells. Glucocorticoids and mineralocorticoids increase vascular tone by up-regulating the receptors of pressor hormones such as angiotensin II (Ang II). Next, we found that physiological concentrations of a cortisol-induced increase in Ang II binding were significantly enhanced by the inhibition of dehydrogenase activity with an antisense DNA complementary to 11betaHSD2 mRNA, and the enhancement was partially but significantly abolished by a selective aldosterone receptor antagonist. This may indicate that impaired dehydrogenase activity in vascular wall results in increased vascular tone by the contribution of cortisol, which acts as a mineralocorticoid. In congenital 11betaHSD deficiency and after the administration of 11betaHSD inhibitors, suppression of dehydrogenase activity in the kidney has been believed to cause renal mineralocorticoid excess, resulting in sodium retention and hypertension. These results show that vascular 11betaHSD activity could influence blood pressure without invoking renal sodium retention. |
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Authors:
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H Hatakeyama; S Inaba; R Takeda; I Miyamori |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Kidney international Volume: 57 ISSN: 0085-2538 ISO Abbreviation: Kidney Int. Publication Date: 2000 Apr |
Date Detail:
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Created Date: 2000-05-09 Completed Date: 2000-05-09 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0323470 Medline TA: Kidney Int Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1352-7 Citation Subset: IM |
Affiliation:
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Third Department of Internal Medicine, Fukui Medical University, Fukui, and KKR Hokuriku Hospital, Kanazawa, Japan. haru@fmsrsa.fukui-med.ac.jp |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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11-beta-Hydroxysteroid Dehydrogenases Angiotensin II / metabolism Cells, Cultured Coronary Vessels / cytology, enzymology*, metabolism Humans Hydrocortisone / pharmacology Hydroxysteroid Dehydrogenases / antagonists & inhibitors, genetics, metabolism* Muscle, Smooth, Vascular / cytology, enzymology, metabolism Oligonucleotides, Antisense / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Oligonucleotides, Antisense; 11128-99-7/Angiotensin II; 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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