Motomura S, Hashimoto K, Hashimoto K
Department of Pharmacology, Yamanashi Medical College, Yamanashi, Japan.
J Cardiovasc Pharmacol. 1987 Dec;10(6):627-35.
Antagonism by Bay k 8644 of the coronary vasodilator and negative inotropic effects of Ca antagonists was simultaneously investigated in the canine isolated, blood-perfused papillary muscle electrically driven at 2 Hz. Drugs were given intraarterially. Continuously infused intraarterially, Bay k 8644 inhibited more predominantly the coronary vasodilator effects of the dihydropyridine Ca antagonists (nifedipine, nitrendipine, and nicardipine) than those of diltiazem and verapamil, or the negative inotropic effects of nifedipine and nitrendipine. The negative inotropic effects of nicardipine, diltiazem, and verapamil were not significantly affected by Bay k 8644. The dose ratio for producing a 50% decrease in developed tension of the papillary muscle over the dose for producing a 50% increase in coronary blood flow (which reflects vascular selectivity) were 41 for nitrendipine, 25 for nifedipine, 21 for nicardipine, 9 for diltiazem, and 7 for verapamil. During infusion by Bay k 8644, the ratio was small (2 to 6) and almost similar among all five Ca antagonists. These results indicate that Bay k 8644 antagonizes more effectively the coronary vasodilating effects of the dihydropyridine Ca antagonists, suggesting that there is a specific type of Ca channel on coronary vascular smooth muscles, through which the dihydropyridine Ca antagonists act.
在以2Hz频率电驱动的犬离体、血液灌注乳头肌中，同时研究了Bay k 8644对钙拮抗剂冠状动脉扩张作用和负性肌力作用的拮抗作用。药物经动脉内给药。经动脉内持续输注时，Bay k 8644对二氢吡啶类钙拮抗剂（硝苯地平、尼群地平和尼卡地平）冠状动脉扩张作用的抑制作用比地尔硫䓬和维拉帕米更显著，对硝苯地平和尼群地平负性肌力作用的抑制作用也更显著。Bay k 8644对尼卡地平、地尔硫䓬和维拉帕米的负性肌力作用无明显影响。使乳头肌舒张张力降低50%的剂量与使冠状动脉血流量增加50%的剂量之比（反映血管选择性），尼群地平为41，硝苯地平为25，尼卡地平为21，地尔硫䓬为9，维拉帕米为7。在Bay k 8644输注期间，该比值较小（2至6），且在所有五种钙拮抗剂中几乎相似。这些结果表明，Bay k 8644能更有效地拮抗二氢吡啶类钙拮抗剂的冠状动脉扩张作用，提示冠状动脉血管平滑肌上存在一种特定类型的钙通道，二氢吡啶类钙拮抗剂通过该通道发挥作用。
