[Increase of the depressive effect of verapamil in acidosis]

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.