Cargnelli G, Bova S, Cannas S, Debetto P, Luciani S
Department of Pharmacology, University of Padua, Italy.
Eur J Pharmacol. 1994 Nov 1;292(1):103-10. doi: 10.1016/0926-6917(94)90032-9.
The effect of amiloride on the positive inotropic and toxic effects of ouabain in guinea-pig left atria has been studied. In atria driven at 1 Hz, amiloride (0.3 and 0.5 mM) decreased the EC50 but did not affect the maximal tension developed by ouabain. At 0.1 Hz, amiloride did not change either the EC50 or the maximal tension developed by ouabain. Ouabain toxicity (onset of arrhythmias) was not changed by amiloride at either frequency of stimulation. Therefore, amiloride did not antagonize either the positive inotropic or the toxic effect of ouabain. The positive inotropic effect of amiloride has been ascribed to the inhibition of the Na+/Ca2+ exchanger. Since amiloride inhibits also the Na+/H+ exchanger, 5-(N-ethyl-N-isopropyl)amiloride (EIPA), an amiloride derivative which selectively inhibits the Na+/H+ exchange, has been tested to evaluate the role of the Na+/H+ exchange in the amiloride-ouabain interaction. EIPA increased the EC50 values of ouabain and decreased the maximal developed tension by the glycoside in atria driven at 0.1 and 1 Hz, but did not antagonize the toxic response (arrhythmias) of atria to ouabain. It is suggested that the inhibition of Ca2+ exit through the Na+/Ca2+ exchange by amiloride and ouabain may explain the observation that the positive inotropic effects of amiloride and ouabain are additive.
研究了氨氯地平对哇巴因在豚鼠左心房中的正性肌力作用和毒性作用的影响。在以1Hz驱动的心房中，氨氯地平（0.3和0.5mM）降低了哇巴因的半数有效浓度（EC50），但不影响哇巴因产生的最大张力。在0.1Hz时，氨氯地平既不改变哇巴因的EC50，也不改变其产生的最大张力。在任何一种刺激频率下，氨氯地平都不会改变哇巴因的毒性（心律失常的发作）。因此，氨氯地平既不拮抗哇巴因的正性肌力作用，也不拮抗其毒性作用。氨氯地平的正性肌力作用归因于对钠/钙交换体的抑制。由于氨氯地平也抑制钠/氢交换体，因此对5-（N-乙基-N-异丙基）氨氯地平（EIPA）进行了测试，EIPA是一种选择性抑制钠/氢交换的氨氯地平衍生物，以评估钠/氢交换在氨氯地平-哇巴因相互作用中的作用。在以0.1Hz和1Hz驱动的心房中，EIPA增加了哇巴因的EC50值，并降低了糖苷产生的最大张力，但不拮抗心房对哇巴因的毒性反应（心律失常）。有人提出，氨氯地平和哇巴因通过抑制钠/钙交换导致的钙离子外流，可能解释了氨氯地平和哇巴因的正性肌力作用具有相加性这一现象。
