EFFECTS OF MIBEFRADIL ON LARGE AND SMALL CORONARY-ARTERIES IN CONSCIOUS DOGS - ROLE OF VASCULAR ENDOTHELIUM

The systemic and coronary hemodynamic effects of mibefradil, a ''nondi hydropyridine'' calcium antagonist acting on both L- and T-type calciu m channels, were investigated in chronically instrumented conscious do gs before and after local endothelium removal of the circumflex corona ry 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, mibefrad il increased the diameter of the left circumflex epicardial coronary a rtery (LCX) by 7.8 +/- 1.2% from 3,006 +/- 219 mu m, 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 a lso reduced by 46% (p < 0.01) the potent coronary constrictor effect o f ergonovine (300 mu g intravenous bolus). These results demonstrate t hat mibefradil is a potent dilator of large and small coronary arterie s in conscious dogs and that similar to 30% of its dilatory effect on large coronary artery is endothelium-independent. In addition, mibefra dil prevents ergonovine-induced epicardial coronary constriction.