Kennedy R H, Seifen E
Eur J Pharmacol. 1987 Aug 4;140(1):85-93. doi: 10.1016/0014-2999(87)90637-6.
This study examined the influence of BAY K-8644, a dihydropyridine Ca2+ agonist, on the positive inotropic effects of strophanthidin, isoproterenol, methoxamine and extracellular Ca2+ (Ca2+0) in atrial muscle isolated from guinea pig heart. BAY K-8644 enhanced both the maximum developed tension observed in the presence of strophanthidin and the sensitivity to its toxic effects. The maximum contractile force observed in the presence of methoxamine was also elevated by BAY K-8644 pretreatment; however, the ED50 value for methoxamine was not affected. The maximum contractile force elicited by BAY K-8644 alone or by strophanthidin or methoxamine in combination with BAY K-8644 was approximately the same as that produced by isoproterenol alone. The Ca2+ agonist did not alter the maximum developed tension elicited by increasing concentrations of isoproterenol or Ca2+0; however, it reduce both the ED50 for Ca2+0 and the concentration of isoproterenol necessary to produce maximum contractility. These results suggest that combinations of BAY K-8644 and cardiac glycosides can elevate contractile force to a level greater than that produced by cardiac glycosides alone.
本研究检测了二氢吡啶类钙离子激动剂BAY K - 8644对从豚鼠心脏分离出的心房肌中，毒毛花苷、异丙肾上腺素、甲氧明及细胞外钙离子（Ca2+0）正性肌力作用的影响。BAY K - 8644增强了在毒毛花苷存在时观察到的最大收缩张力及其对毒性作用的敏感性。BAY K - 8644预处理也提高了在甲氧明存在时观察到的最大收缩力；然而，甲氧明的半数有效剂量（ED50）值未受影响。单独使用BAY K - 8644或毒毛花苷或甲氧明与BAY K - 8644联合使用所引发的最大收缩力，与单独使用异丙肾上腺素所产生的最大收缩力大致相同。钙离子激动剂并未改变因异丙肾上腺素或Ca2+0浓度增加所引发的最大收缩张力；然而，它降低了Ca2+0的ED50以及产生最大收缩力所需的异丙肾上腺素浓度。这些结果表明，BAY K - 8644与强心苷的组合可将收缩力提高到高于单独使用强心苷所产生的水平。
