Relaxation of large coronary artery by verapamil, D600, and nifedipine is constrictor selective: comparison with glyceryl trinitrate

Abstract

We compared the vasodilator potencies of a number of Ca2+-entry blockers with glyceryl trinitrate (GTN) in isolated ring segments of dog coronary arteries contracted by a variety of substances. Rings were contracted to 80% of maximum by serotonin, phenylephrine (PE), noradrenaline (NA), K+ (KCl), or U46619 (stable thromboxane A2 analogue). Cumulative additions of a vasodilator then relaxed the ring towards basal tone. GTN had a similar IC50 value (0.1 - 0.3 microM) regardless of the substance used to contract the ring. In contrast, nifedipine and verapamil were weak relaxant drugs against arteries contracted by U46619. Nifedipine was most potent in rings contracted by K+, whereas verapamil was similarly effective towards K+ and serotonin, but threefold less potent against PE or NA. The (-)enantiomers of verapamil and D600 were more potent (seven-to 26-fold) than the (+)enantiomers in arteries contracted by K+ or serotonin, but not for PE or NA. A combination of (-)verapamil and GTN showed additive effects without a change in the IC50 for GTN. We conclude that, in contrast with GTN, the effectiveness of Ca2+-entry blockers in the treatment of coronary vasospasm may be dependent on the nature of the constrictor signal.