Gende O A, Camilión de Hurtado M C
Acta Physiol Pharmacol Latinoam. 1986;36(4):369-76.
The effect of pH on the negative chronotropic response to slow channel blockers was studied in isolated rat atria incubated at pH 7.39 (control group) and at pH 7.03 (group in acidosis). Cumulative concentration-response curves for verapamil, nitrendipine and nifedipine were done recording the spontaneous electrical activity 20 min after each drug addition. Both verapamil and dihydropyridines produced a depression of sinoatrial automatism, but only verapamil showed an enhanced effect in acidosis. The change in atrial rate was significantly greater in acidosis than in the control group with verapamil concentrations from 3 X 10(-9) to 10(-7) M. This enhancement of the negative chronotropic effect of verapamil by acidosis resembles a similar modification to the one observed in the inotropic response. Our experiments suggest a synergistic mechanism in the inhibition of Ca2+ channels by H+ and verapamil, but not for H+ and dihydropyridines.
在pH 7.39（对照组）和pH 7.03（酸中毒组）孵育的离体大鼠心房中，研究了pH对慢通道阻滞剂负性变时反应的影响。在每次添加药物20分钟后记录自发电活动，绘制维拉帕米、尼群地平和硝苯地平的累积浓度-反应曲线。维拉帕米和二氢吡啶类药物均使窦房结自律性降低，但只有维拉帕米在酸中毒时显示出增强效应。当维拉帕米浓度为3×10⁻⁹至10⁻⁷ M时，酸中毒时心房率的变化明显大于对照组。酸中毒增强维拉帕米的负性变时效应类似于在变力反应中观察到的类似改变。我们的实验表明，H⁺和维拉帕米在抑制Ca²⁺通道方面存在协同机制，但H⁺和二氢吡啶类药物之间不存在这种机制。
