Effect of calcium antagonists on vascular responses of bovine coronary artery to acetylcholine, noradrenaline, and 5-hydroxytryptamine.

Verapamil (0.05-5 microM), diltiazem (0.2-20 microM), and nifedipine (0.3-30 microM) produced concentration-dependent relaxation of bovine coronary artery. Based on the EC50 values (concentration to produce 50% maximum response), the calcium entry blocker verapamil (relative potency = 1) was 3.4 and 7 times as potent as diltiazem and nifedipine, respectively, in producing relaxation of bovine coronary artery. In addition, verapamil reduced the contractions produced by acetylcholine (0.01-10 microM), 5-hydroxytryptamine (5-HT) (0.01-10 microM) whereas it potentiated the relaxation produced by noradrenaline (0.01-10 microM). It was concluded that verapamil, diltiazem, and nifedipine (a) relax the bovine coronary artery, verapamil being more potent than diltiazem and nifedipine, and (b) the calcium entry blockers modified the contractile responses to neurotransmitter agents, acetylcholine, noradrenaline, and 5-HT, inhibiting the contractions produced by acetylcholine and 5-HT, and enhancing the relaxation produced by noradrenaline.