Document Detail

Therapeutic effects of vitamin D analogs on cardiac hypertrophy in spontaneously hypertensive rats.
MedLine Citation:
PMID:  20616348     Owner:  NLM     Status:  MEDLINE    
Vitamin D inhibits renin expression and blocks the compensatory induction of renin associated with the use of renin-angiotensin system inhibitors. Here we test the therapeutic effects of two commonly used vitamin D analogs and their combination with losartan on the development of left ventricular hypertrophy. One-month-old male spontaneously hypertensive rats were treated with vehicle, losartan, paricalcitol, doxercalciferol, a combination of losartan and paricalcitol, or a combination of losartan and doxercalciferol for 2 months. Blood pressure was markedly reduced by losartan, but not by paricalcitol or doxercalciferol alone. Echocardiograpy demonstrated a 65 to 80% reduction in left ventricular wall thickness with losartan, paricalcitol, or doxercalciferol monotherapy and almost complete prevention of left ventricular hypertrophy with the combination therapies. Attenuation of cardiac and cardiomyocyte hypertrophy, and suppression of atrial and brain natriuretic peptides, were most marked in the combination therapy groups. These changes were well correlated with left ventricular gene and microRNA expression profiles in the different treatment groups. Renal and cardiac renin expression was markedly increased in losartan-treated animals, but nearly normalized with combination therapy. The same vitamin D analogs suppressed plasma renin activity in patients receiving chronic hemodialysis. These data demonstrate that vitamin D analogs have potent antihypertrophic activity in part via suppression of renin in the kidney and heart, and combination of these analogs with losartan achieves much better therapeutic effects because of the blockade of the compensatory renin increase.
Juan Kong; Gene H Kim; Minjie Wei; Tao Sun; George Li; Shu Q Liu; Xinmin Li; Ishir Bhan; Qun Zhao; Ravi Thadhani; Yan Chun Li
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-07-08
Journal Detail:
Title:  The American journal of pathology     Volume:  177     ISSN:  1525-2191     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-08-03     Completed Date:  2011-01-25     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  622-31     Citation Subset:  AIM; IM    
Laboratory of Metabolic Disease Research and Drug Development, Shengjing Hospital, China Medical University, Shenyang, China.
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MeSH Terms
Antihypertensive Agents / therapeutic use
Ergocalciferols / therapeutic use*
Hypertrophy, Left Ventricular / drug therapy*,  pathology
Losartan / therapeutic use
Microarray Analysis
Middle Aged
Random Allocation
Rats, Inbred SHR*
Renin / blood
Vitamin D* / analogs & derivatives,  therapeutic use
Vitamins / therapeutic use
Grant Support
Reg. No./Substance:
0/Antihypertensive Agents; 0/Ergocalciferols; 0/Vitamins; 114798-26-4/Losartan; 131918-61-1/paricalcitol; 1406-16-2/Vitamin D; 54573-75-0/1 alpha-hydroxyergocalciferol; EC

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