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 flow (CBF) without decreasing aortic blood pressure (AoP) with ischemic and nonischemic hearts, and whether the presence of cellular acidosis in ischemic myocardium contributes to the augmentation of coronary vasodilation due to nisoldipine. In 42 dogs, coronary perfusion pressure (CPP) was reduced so that CBF decreased to 60% of the baseline, and CPP was maintained constant thereafter. First, we administered nisoldipine into a systemic vein in the ischemic and nonischemic hearts. Second, nisoldipine was administered into the canine coronary artery of the ischemic myocardium, with and without administration of either sodium bicarbonate (NaHCO3), sodium hydroxide (NaOH), or amiloride. Nisoldipine (0.25-4.0 mg/kg, i.v.) increased CBF 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 increases in fractional shortening (FS; 11 +/- 2% to 21 +/- 2%) and lactate extraction ratio (LER; -19 +/- 4% to 15 +/- 2%). Increases in CBF, FS, and LER were markedly attenuated during administration of nisoldipine with concomitant administration of either NaHCO3 or NaOH. Furthermore, the extent of increases 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 amiloride. We conclude that myocardial cellular acidosis plays an important role in mediating coronary vasodilation affected by nisoldipine in the ischemic myocardium. H+ may modulate the property of voltage-dependent Ca channels via Na(+)-H+ exchange.
First Department of Medicine, Osaka University School of Medicine, Suita, Japan. Kitakaze@medone.med.osaka-u.ac.jp
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Kitakaze
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Funaya
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Komamura
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Node
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Minamino
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Mori
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Takeda
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Kuzuya
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Hori
D000138:Acidosis / Q000503:physiopathology*; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002021:Buffers; D003326:Coronary Circulation / Q000187:drug effects*; D004232:Diuretics / Q000494:pharmacology; D004285:Dogs; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D015737:Nisoldipine / Q000627:therapeutic use*; D010100:Oxygen / Q000097:blood; D014665:Vasodilator Agents / Q000627:therapeutic use*
D001639:Bicarbonates; D002021:Buffers; D004232:Diuretics; D014665:Vasodilator Agents; D015737:Nisoldipine; D000584:Amiloride; D010100:Oxygen