Sensitivity of cat papillary muscles to verapamil and nifedipine: enhanced effect in acidosis

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Abstract
The effects of acidosis on the myocardial sensitivity to verapamil and nifedipine were examined by measuring the changes in tension in cat papillary muscles perfused in oxygenated physiological saline. Calcium concentration was altered over a range of 2 to 12 mmol·litre−1 and pH adjusted to 7.4, 6.8 or 6.0. Addition of verapamil or nifedipine moved the calcium dose response to the right. At pH 7.4 a Schild plot confirmed competitive interaction between verapamil and calcium, with a calculated dissociation constant (KB) for verapamil of 4.6±0.2 μg·cm−3. At pH 6.0, the slope was less than 1.0 (not significant, P=0.2) but KB was significantly lower (Pμg·cm−3. Similar enhancement of sensitivity by lowered pH was found for nifedipine. It is proposed that partial inhibition of the slow channel by acidosis increases the sensitivity to calcium entry blockers. This might create a differential effect between normal and diseased tissue in vivo.