Brown L, Cragoe E J, Abel K C, Manley S W, Bourke J R
Department of Physiology and Pharmacology, University of Queensland, Brisbane, Australia.
Naunyn Schmiedebergs Arch Pharmacol. 1991 Aug;344(2):220-4. doi: 10.1007/BF00167222.
The role of inhibition of Na+/Ca2+ exchange in the positive inotropic, negative chronotropic and vasorelaxant responses to amiloride and some of its analogues was investigated in isolated cardiovascular tissues from female Wistar rats. The compounds tested were amiloride, 5-(N-ethyl-N-isopropyl)amiloride (EIPA, a potent inhibitor of Na+/H+ exchange), phenamil and 2',4'-dimethylbenzamil (DMB), both potent Na+ channel inhibitors with activity against Na+/Ca2+ exchange, and 5-(N-4-chlorobenzyl)-2',4'-dimethylbenzamil (CBDMB), a potent inhibitor of Na+/Ca2+ exchange with reduced activity against Na+ channels compared with its parent compound DMB. Phenamil, DMB and CBDMB increased the force of contraction of right ventricular papillary muscles with similar potencies (-log EC50 values: 4.77 +/- 0.06, 5.09 +/- 0.09, 4.97 +/- 0.17 respectively), while amiloride and EIPA gave small negative inotropic responses. All compounds gave negative chronotropic responses at similar concentrations to those which exerted inotropic effects. Inhibition of KCl contraction of endothelium-free aortic rings was observed with all compounds tested. Phenamil, DMB and CBDMB but not amiloride or EIPA showed a shift to the left of the concentration-response curves in the presence of intact endothelium. These results provide further evidence for positive inotropic and endothelium-dependent vasorelaxant effects of amiloride analogues mediated by inhibition of Na+/Ca2+ exchange.
在雌性Wistar大鼠的离体心血管组织中，研究了抑制钠/钙交换在对阿米洛利及其一些类似物的正性肌力、负性变时和血管舒张反应中的作用。所测试的化合物有阿米洛利、5-(N-乙基-N-异丙基)阿米洛利（EIPA，一种有效的钠/氢交换抑制剂）、非那明和2',4'-二甲基苯甲酰胺（DMB），二者均为有效的钠通道抑制剂且具有抗钠/钙交换活性，还有5-(N-4-氯苄基)-2',4'-二甲基苯甲酰胺（CBDMB），一种有效的钠/钙交换抑制剂，与母体化合物DMB相比，其对钠通道的活性降低。非那明、DMB和CBDMB以相似的效力增加右心室乳头肌的收缩力（-log EC50值分别为：4.77±0.06、5.09±0.09、4.97±0.17），而阿米洛利和EIPA产生较小的负性肌力反应。所有化合物在产生变力作用的相似浓度下均产生负性变时反应。在所测试的所有化合物中均观察到对无内皮主动脉环氯化钾收缩的抑制作用。在完整内皮存在的情况下，非那明、DMB和CBDMB而非阿米洛利或EIPA显示浓度-反应曲线向左移动。这些结果为阿米洛利类似物通过抑制钠/钙交换介导的正性肌力和内皮依赖性血管舒张作用提供了进一步的证据。
