Effect of flunarizine on calcium-induced responses of peripheral vascular smooth muscle

Flunarizine, a difluoro derivative of cinnarizine, is a potent inhibitor of Ca2+-induced constriction of isolated arteries; this inhibition has a gradual onset and a prolonged duration. The present study demonstrates that flunarizine inhibits Ca2+-induced responses in the rat tail and the rabbit ear arteries, but not in isolated cat papillary muscle; flunarizine does not depress the spontaneous rhythmic activity of the rat portal-mesenteric vein. This dissociation between the arterial preparations on the one hand, was less pronounced with cinnarizine, and was not seen with verapamil and papaverine. The present experiments thus suggest that flunarizine inhibits peripheral vasoconstriction by selectively decreasing the rate of stimulated Ca2+-influx, without affecting the myogenic activity of the vascular smooth muscle cells.