Document Detail

1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system.
MedLine Citation:
PMID:  12122115     Owner:  NLM     Status:  MEDLINE    
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.
Yan Chun Li; Juan Kong; Minjie Wei; Zhou-Feng Chen; Shu Q Liu; Li-Ping Cao
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  110     ISSN:  0021-9738     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2002 Jul 
Date Detail:
Created Date:  2002-07-17     Completed Date:  2002-08-14     Revised Date:  2014-04-11    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  229-38     Citation Subset:  AIM; IM    
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MeSH Terms
Angiotensin II / blood
Calcitriol / biosynthesis,  pharmacology*
Drinking Behavior / physiology
Gene Expression / drug effects
Hypertension / etiology,  genetics,  physiopathology
Hypocalcemia / genetics,  metabolism
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
Reg. No./Substance:
0/Neuropeptides; 0/RNA, Messenger; 0/Receptors, Calcitriol; 0/Sodium, Dietary; 0/Trans-Activators; 11128-99-7/Angiotensin II; EC; FXC9231JVH/Calcitriol
Comment In:
J Clin Invest. 2002 Jul;110(2):155-6   [PMID:  12122105 ]
Clin Chem. 2014 Mar;60(3):561-2   [PMID:  24363372 ]

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