Nisoldipine selectively induces coronary vasodilation and improves mild myocardial ischemia in dogs: A potential role of cellular acidosis

We examined whether nisoldipine, a calcium (Ca) channel blocker, increases coronary blood dow (CBF) without decreasing aortic blood pressure (AoP) wit h ischemic and nonischemic hearts, and whether the presence of cellular aci dosis in ischemic myocardium contributes to the augmentation of coronary va sodilation due to nisoldipine. In 42 dogs, coronary perfusion pressure (CPP ) was reduced so that CBF decreased to 60% of the baseline, and CPP was mai ntained constant thereafter. First, we administered nisoldipine into a syst emic vein in the ischemic and nonischemic hearts. Second, nisoldipine was a dministered into the canine coronary artery of the ischemic myocardium with and without administration of either sodium bicarbonate (NaHCO3), sodium h ydroxide (NaOH), or amiloride. Nisoldipine (0.25-4.0 mg/kg, IV) increased C BF by 59% in the ischemic myocardium more than the nonischemic myocardium ( by 34%) without reducing AoP. The infusion of nisoldipine (40 ng/kg/min, IC ) increased CBF markedly by about 55% in the ischemic myocardium with incre ases in fractional shortening (FS; 11 +/- 2% to 21 +/- 2%) and lactate extr action ratio (LER; -19 +/- 4% to 15 +/- 2%). Increases in CBF, FS, and LER were markedly attenuated during administration of nisoldipine with concomit ant administration of either NaHCO3 or NaOH. Furthermore, the extent of inc reases in CBF (54 +/- 2 mL/100 g/min), FS (13 +/- 2%), and LER(-17 +/- 4%) were also markedly attenuated due to the concomitant treatment with amilori de. We conclude that myocardial cellular acidosis plays an important role i n mediating coronary vasodilation affected by nisoldipine in the ischemic m yocardium. H+ may modulate the property of voltage-dependent Ca channels vi a Na+-H+ exchange.