Document Detail

Ca(2+) channel blocker benidipine promotes coronary angiogenesis and reduces both left-ventricular diastolic stiffness and mortality in hypertensive rats.
MedLine Citation:
PMID:  20543715     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: The beneficial cardiac effects of some Ca(2+) channel blockers have been attributed to blood pressure reduction, but these pleiotropic effects require further investigation. We compared the effects of benidipine, which has beneficial cardiac effects, and nitrendipine, which does not, in an animal model of hypertensive diastolic heart failure (DHF).
METHODS AND RESULTS: Male Dahl salt-sensitive rats were fed a high-salt diet from age 7 weeks to induce hypertension and were either vehicle or orally administered benidipine (3 mg/kg daily) or nitrendipine (10 mg/kg daily) from age 10 to 18 weeks. Control rats were maintained on a low-salt diet. In vehicle-treated rats, left-ventricular (LV) fractional shortening was preserved but LV end-diastolic pressure was increased, indicative of DHF. Benidipine and nitrendipine had similar antihypertensive effects and reduced both LV weight and cardiomyocyte hypertrophy. Benidipine reduced LV diastolic stiffness and mortality to a greater extent than did nitrendipine. Benidipine, but not nitrendipine, also reduced lung weight. The extent of interstitial fibrosis and the abundance of mRNAs for prohypertrophic, profibrotic, or proinflammatory genes in the left ventricle were reduced by benidipine and nitrendipine. Benidipine, but not nitrendipine, increased capillary density and restored the expression of hypoxia-inducible factor 1alpha, vascular endothelial growth factor, and endothelial nitric oxide synthase in the left ventricle.
CONCLUSIONS: Benidipine reduced LV diastolic stiffness and increased survival, effects likely attributable predominantly to promotion of coronary angiogenesis rather than to attenuation of interstitial fibrosis. Benidipine may thus be more effective than purely L-type Ca(2+) channel blockers in preventing hypertensive DHF.
Takao Nishizawa; Xian Wu Cheng; Zhehu Jin; Koji Obata; Kohzo Nagata; Akihiro Hirashiki; Takeshi Sasaki; Akiko Noda; Kyosuke Takeshita; Hideo Izawa; Guo-Ping Shi; Masafumi Kuzuya; Kenji Okumura; Toyoaki Murohara
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of hypertension     Volume:  28     ISSN:  1473-5598     ISO Abbreviation:  J. Hypertens.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-06-24     Completed Date:  2010-12-17     Revised Date:  2014-09-19    
Medline Journal Info:
Nlm Unique ID:  8306882     Medline TA:  J Hypertens     Country:  England    
Other Details:
Languages:  eng     Pagination:  1515-26     Citation Subset:  IM    
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MeSH Terms
Antihypertensive Agents / pharmacology,  therapeutic use
Calcium Channel Blockers / pharmacology*
Coronary Circulation / drug effects*
Diastole / drug effects
Dihydropyridines / pharmacology*
Heart Failure / drug therapy,  metabolism,  physiopathology
Heart Ventricles / drug effects*,  metabolism,  physiopathology
Hypertension / drug therapy*,  mortality,  physiopathology
Neovascularization, Physiologic / drug effects*
Nitrendipine / pharmacology,  therapeutic use
Rats, Inbred Dahl
Grant Support
R01 HL060942/HL/NHLBI NIH HHS; R01 HL060942-12/HL/NHLBI NIH HHS; R01 HL081090/HL/NHLBI NIH HHS; R01 HL081090-04/HL/NHLBI NIH HHS; R01 HL088547/HL/NHLBI NIH HHS; R01 HL088547-04/HL/NHLBI NIH HHS
Reg. No./Substance:
0/Antihypertensive Agents; 0/Calcium Channel Blockers; 0/Dihydropyridines; 4G9T91JS7E/benidipine; 9B627AW319/Nitrendipine

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