Kennedy R H, Berlin J R, Ng Y C, Akera T, Brody T M
J Mol Cell Cardiol. 1986 Feb;18(2):177-88. doi: 10.1016/s0022-2828(86)80470-9.
The direct effects of amiloride on myocardial contractility were examined in electrically stimulated left atrial muscle of guinea-pig heart. Amiloride (0.3 to 1.5 mM) produced a positive inotropic effect which, at higher concentrations, was followed by a decline in developed tension. These effects were not accompanied by contracture or arrhythmia and were not affected by a combination of phentolamine, nadolol, cimetidine, tripelennamine and atropine. The above concentrations of amiloride prolonged the action potential duration during the development of the positive inotropic effect; however, no further change in the action potential duration was observed during the decline in developed tension caused by high concentrations of amiloride. Myocardial membrane Na,K-ATPase, ouabain-sensitive 86Rb+ uptake and Na+-dependent Ca2+ efflux from sarcolemmal membrane vesicles were all inhibited by amiloride. The positive inotropic effect of the agent is reduced and the negative inotropic action is enhanced in low Na+ solutions, i.e., under conditions likely to favor Ca2+ influx via Na+/Ca2+ exchange. These results suggest that amiloride, under the present conditions, has a complex interaction with cardiac muscle fibers. Amiloride may produce its inotropic effects in guinea-pig atrial muscle by several mechanisms including sodium pump inhibition, Na+/Ca2+ exchange inhibition, prolongation of the action potential duration, and/or actions such as Na+/H+ exchange inhibition which were not directly addressed in this study.
在豚鼠心脏电刺激的左心房肌中研究了氨氯地平对心肌收缩性的直接作用。氨氯地平（0.3至1.5 mM）产生正性肌力作用，在较高浓度时，随后出现舒张张力下降。这些作用不伴有挛缩或心律失常，且不受酚妥拉明、纳多洛尔、西咪替丁、曲吡那敏和阿托品联合使用的影响。上述浓度的氨氯地平在产生正性肌力作用期间延长动作电位持续时间；然而，在高浓度氨氯地平引起的舒张张力下降期间，未观察到动作电位持续时间有进一步变化。氨氯地平抑制心肌膜Na，K - ATP酶、哇巴因敏感的86Rb +摄取以及肌膜囊泡中Na +依赖性Ca2 +外流。在低Na +溶液中，即在可能有利于通过Na + / Ca2 +交换使Ca2 +内流的条件下，该药物的正性肌力作用减弱，负性肌力作用增强。这些结果表明，在目前条件下，氨氯地平与心肌纤维有复杂的相互作用。氨氯地平可能通过几种机制在豚鼠心房肌中产生其肌力作用，包括抑制钠泵、抑制Na + / Ca2 +交换、延长动作电位持续时间和/或抑制Na + / H +交换等作用，本研究未直接涉及这些作用。
