| 1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system. | |
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MedLine Citation:
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PMID: 12122115 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Inappropriate activation of the renin-angiotensin system, which plays a central role in the regulation of blood pressure, electrolyte, and volume homeostasis, may represent a major risk factor for hypertension, heart attack, and stroke. Mounting evidence from clinical studies has demonstrated an inverse relationship between circulating vitamin D levels and the blood pressure and/or plasma renin activity, but the mechanism is not understood. We show here that renin expression and plasma angiotensin II production were increased severalfold in vitamin D receptor-null (VDR-null) mice, leading to hypertension, cardiac hypertrophy, and increased water intake. However, the salt- and volume-sensing mechanisms that control renin synthesis are still intact in the mutant mice. In wild-type mice, inhibition of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] synthesis also led to an increase in renin expression, whereas 1,25(OH)(2)D(3) injection led to renin suppression. We found that vitamin D regulation of renin expression was independent of calcium metabolism and that 1,25(OH)(2)D(3) markedly suppressed renin transcription by a VDR-mediated mechanism in cell cultures. Hence, 1,25(OH)(2)D(3) is a novel negative endocrine regulator of the renin-angiotensin system. Its apparent critical role in electrolytes, volume, and blood pressure homeostasis suggests that vitamin D analogues could help prevent or ameliorate hypertension. |
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Authors:
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Yan Chun Li; Juan Kong; Minjie Wei; Zhou-Feng Chen; Shu Q Liu; Li-Ping Cao |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The Journal of clinical investigation Volume: 110 ISSN: 0021-9738 ISO Abbreviation: J. Clin. Invest. Publication Date: 2002 Jul |
Date Detail:
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Created Date: 2002-07-17 Completed Date: 2002-08-14 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 7802877 Medline TA: J Clin Invest Country: United States |
Other Details:
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Languages: eng Pagination: 229-38 Citation Subset: AIM; IM |
Affiliation:
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Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA. cyan@medicine.bsd.uchicago.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Angiotensin II
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blood Animals Calcitriol / biosynthesis, pharmacology* Drinking Behavior / physiology Gene Expression / drug effects Hypertension / etiology, genetics, physiopathology Hypocalcemia / genetics, metabolism Mice Mice, Knockout Neuropeptides / deficiency, genetics Promoter Regions, Genetic / drug effects RNA, Messenger / genetics, metabolism Receptors, Calcitriol / deficiency, genetics Renin / genetics Renin-Angiotensin System / drug effects*, genetics, physiology Signal Transduction Sodium, Dietary / administration & dosage Trans-Activators / deficiency, genetics |
| Grant Support | |
ID/Acronym/Agency:
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DK-42086/DK/NIDDK NIH HHS; DK-59327/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Neuropeptides; 0/RNA, Messenger; 0/Receptors, Calcitriol; 0/Sodium, Dietary; 0/Trans-Activators; 11128-99-7/Angiotensin II; 32222-06-3/Calcitriol; EC 3.4.23.15/Renin |
| Comments/Corrections | |
Comment In:
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J Clin Invest. 2002 Jul;110(2):155-6
[PMID:
12122105
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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