Document Detail

Effects of mibefradil on large and small coronary arteries in conscious dogs: role of vascular endothelium.
MedLine Citation:
PMID:  8856484     Owner:  NLM     Status:  MEDLINE    
The systemic and coronary hemodynamic effects of mibefradil, a "nondihydropyridine" calcium antagonist acting on both L- and T-type calcium channels, were investigated in chronically instrumented conscious dogs before and after local endothelium removal of the circumflex coronary artery by angioplasty. After intravenous infusion, mibefradil (0.2 mg kg-1 min-1) decreased mean arterial blood pressure (MAP; -15 +/- 1%), increased heart rate (HR; 58 +/- 9%), and coronary blood flow (CBF; 103 +/- 14%) (all p < 0.05). Before endothelium removal, mibefradil increased the diameter of the left circumflex epicardial coronary artery (LCX) by 7.8 +/- 1.2% from 3,006 +/- 219 microns, but this dilatory effect was significantly reduced by 69% (p < 0.001) and 45% (p < 0.01), 3 and 21 days after endothelium removal, respectively. Mibefradil also reduced by 46% (p < 0.01) the potent coronary constrictor effect of ergonovine (300 micrograms intravenous bolus). These results demonstrate that mibefradil is a potent dilator of large and small coronary arteries in conscious dogs and that approximately 30% of its dilatory effect on large coronary artery is endothelium-independent. In addition, mibefradil prevents ergonovine-induced epicardial coronary constriction.
D Karila-Cohen; J L Dubois-Randé; J F Giudicelli; A Berdeaux
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  28     ISSN:  0160-2446     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  1996 Aug 
Date Detail:
Created Date:  1997-03-25     Completed Date:  1997-03-25     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  271-7     Citation Subset:  IM    
Départment de Pharmacologie, Faculté de Médecine Paris-Sud, France.
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MeSH Terms
Benzimidazoles / pharmacology*
Blood Pressure / drug effects
Calcium Channel Blockers / pharmacology*
Coronary Circulation / drug effects
Coronary Vessels / drug effects*
Endothelium, Vascular / drug effects*
Ergonovine / antagonists & inhibitors,  pharmacology
Heart Rate / drug effects
Tetrahydronaphthalenes / pharmacology*
Vasodilation / drug effects
Vasodilator Agents / pharmacology*
Reg. No./Substance:
0/Benzimidazoles; 0/Calcium Channel Blockers; 0/Tetrahydronaphthalenes; 0/Vasodilator Agents; 116644-53-2/Mibefradil; 60-79-7/Ergonovine

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