Specificity of action of Ca++ entry blockers. A comparison of their actions in rat arteries and in human coronary arteries.

Among the large number of compounds which inhibit the contraction evoked by calcium in depolarized smooth muscle, calcium entry blockers are those that specifically block calcium entry during muscle activation. They affect neither Ca++ efflux nor intracellular Ca++ release. A comparative study of the diphenylpiperazines, cinnarizine and flunarizine, with the dihydropyridine, nifedipine, allows conclusions to be drawn as to their specificity of action. We have also examined the action of calcium entry blockers, considering tissue and stimulus selectivity. The inhibition of smooth muscle contraction can be quantitatively related to blockade of Ca++ influx. In rat aorta and mesenteric arteries, the potency of Ca++ entry blockers depends on the stimulus in the following order of sensitivity: K depolarization greater norepinephrine greater than PGF2 alpha. As far as flunarizine, but not nifedipine, is concerned, the activity is higher in mesenteric arteries than in aorta. This raises the possibility that calcium channels have receptor and organ specificity, a hypothesis which is supported by the observation that the order of potency of several calcium entry blockers is different in various vessels including human coronary arteries, and that the action of the blockers increases with the age of the patient.