Document Detail


Cardiac hypertrophy in vitamin D receptor knockout mice: role of the systemic and cardiac renin-angiotensin systems.
MedLine Citation:
PMID:  15367398     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Our recent studies suggest that 1,25-dihydroxyvitamin D3 functions as an endocrine suppressor of renin biosynthesis. Genetic disruption of the vitamin D receptor (VDR) results in overstimulation of the renin-angiotensin system (RAS), leading to high blood pressure and cardiac hypertrophy. Consistent with the higher heart-to-body weight ratio, the size of left ventricular cardiomyocytes in VDR knockout (KO) mice was markedly increased compared with wild-type (WT) mice. As expected, levels of atrial natriuretic peptide (ANP) mRNA and circulating ANP were also increased in VDRKO mice. Treatment of VDRKO mice with captopril reduced cardiac hypertrophy and normalized ANP expression. To investigate the role of the cardiac RAS in the development of cardiac hypertrophy, the expression of renin, angiotensinogen, and AT-1a receptor in the heart was examined by real-time RT-PCR and immunostaining. In VDRKO mice, the cardiac renin mRNA level was significantly increased, and this increase was further amplified by captopril treatment. Consistently, intense immunostaining was detected in the left ventricle of captopril-treated WT and VDRKO mice by use of an anti-renin antibody. Levels of cardiac angiotensinogen and AT-1a receptor mRNAs were unchanged in the mutant mice. These data suggest that the cardiac hypertrophy seen in VDRKO mice is a consequence of activation of both the systemic and cardiac RAS and support the notion that 1,25-dihydroxyvitamin D(3) regulates cardiac functions, at least in part, through the RAS.
Authors:
Wei Xiang; Juan Kong; Songcang Chen; Li-Ping Cao; Guilin Qiao; Wei Zheng; Wenhua Liu; Xinmin Li; David G Gardner; Yan Chun Li
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2004-09-14
Journal Detail:
Title:  American journal of physiology. Endocrinology and metabolism     Volume:  288     ISSN:  0193-1849     ISO Abbreviation:  Am. J. Physiol. Endocrinol. Metab.     Publication Date:  2005 Jan 
Date Detail:
Created Date:  2004-12-08     Completed Date:  2005-03-02     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  100901226     Medline TA:  Am J Physiol Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E125-32     Citation Subset:  IM    
Affiliation:
Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antihypertensive Agents / pharmacology
Atrial Natriuretic Factor / metabolism
Captopril / pharmacology
Cardiomegaly / pathology,  physiopathology*
Mice
Mice, Knockout
Myocytes, Cardiac / pathology,  physiology
Receptors, Calcitriol / genetics*
Renin-Angiotensin System / drug effects,  physiology*
Grant Support
ID/Acronym/Agency:
DK-59327/DK/NIDDK NIH HHS; DK-62027/DK/NIDDK NIH HHS; HL-35753/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antihypertensive Agents; 0/Receptors, Calcitriol; 62571-86-2/Captopril; 85637-73-6/Atrial Natriuretic Factor

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


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