Effect of a new vasodilator, pinacidil (P 1134), on potassium, noradrenaline and serotonin induced contractions in rabbit vascular tissues.

Ring preparations of rabbit aorta were contracted by potassium (127 mM). Pinacidil (P 1134), a new vasodilator ( 2.3 x 10(-5) M), the calcium antagonists verapamil (3.4 x 10(-7) M), nifedipine (3.4 x 10(-9) M) and hydralazine (1.9 x 10(-4) M) relaxed the preparation by 50%. 50% relaxation of noradrenaline-contracted tissues was obtained with pinacidil, 6.8 x 10(-5) M, verapamil, 2.4 x 10(-3) M. At 2 x 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 x 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 x 10(-5) M and verapamil, 2.0 x 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 x 10(-4) M and by verapamil, 8.8 x 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.