Effect of a New Vasodilator, Pinacidil (P 1134), on Potassium, Noradrenaline and Serotonin Induced Contractions in Rabbit Vascular Tissues

Abstract

Ring preparations of rabbit aorta were contracted by K+ (127 mM). Pinacidil (P 1134), a new vasodilator (2.3 .times. 10-2 M), the Ca antagonists verapamil (3.4 .times. 10-4 M), nifedipine (3.4 .times. 10-9 M) and hydralazine (1.9 .times. 102 M) relaxed the preparation by 50%; 50% relaxation of noradrenaline [norepinephrine] contracted tissues was obtained with pinacidil 6.8 .times. 10-5 M, verapamil 2.4 .times. 10-54 M and hydralazine 1.9 .times. 10-3 M. At 2 .times. 10-7 M concentration nifedipine was almost inactive. In ring preparations of rabbit aorta exposed to Ca-free medium and then depolarized with K+ (127 mM), pinacidil 5 .times. 10-5 M and nifedipine 10-8 M significantly inhibited the contractions by cumulative Ca addition. Hydralazine 10-3 M had no effect. Noradrenaline-induced contractions in Ca-free medium or in presence of increasing amounts of Ca were significantly inhibited by nifedipine 10-8 M and hydralazine 10-3 M. Pinacidil 10-4 M had no effect. Pinacidil 1.3 .times. 10-5 M and verapamil 2.0 .times. 10-5 M inhibited by 50% the serotonin-induced increase of perfusion pressure of isolated rabbit ear artery. The noradrenaline effect in this preparation were 50% inhibited by pinacidil 2.4 .times. 10-4 M and by verapamil 8.8 .times. 10-5 M. Hydralazine 10-3 M exerted minor inhibitory effect. Evidently, interference with Ca influx contributes to the vasodilator activity of pinacidil.