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 potassium (127 mM). Pinacidil (P 1134), a new vasodilator (2.3×10−5 M), the calcium antagonists verapamil (3.4×10−7 M), nifedipine (3.4×10−9 M) and hydralazine (1.9×104 M) relaxed the preparation by 50%. 50% relaxation of noradrenaline‐contracted tissues was obtained with pinacidil, 6.8×10−5 M, verapamil, 2.4×10−4 M and hydralazine, 1.9×10−3 M. At 2×10−7 M concentration nifedipine was almost inactive. In ring preparations of rabbit aorta exposed to calcium‐free medium and then depolarized with potassium (127 mM), pinacidil, 5×10−5 M and nifedipine, 10−8 M significantly inhibited the contractions by cumulative addition of calcium. Hydralazine, 10−3 M had no effect. Noradrenaline‐induced contractions in calcium‐free medium or in presence of increasing amounts of calcium were significantly inhibited by nifedipine, 10−8 M and hydralazine, 10−3 M. Pinacidil, 10−4 M had no effect. Pinacidil, 1.3×10−5 M and verapamil, 2.0×10−5 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, 2.4×10−4 M and by verapamil, 8.8×10−5 M. Hydralazine, 10−3 M exerted minor inhibitory effect. It is suggested that interference with calcium influx contributes to the vasodilator activity of pinacidil.