A comparison of the inhibitory effect of cinnarizine and papaverine on the noradrenaline- and calcium-evoked contraction of isolated rabbit aorta and mesenteric arteries.

The inhibitory effects of cinnarizine and papaverine on the noradrenaline- and Ca-induced contraction of the rabbit thoracic aorta and mesenteric arteries have been compared. Papaverine was equally effective in reducing the contractile response evoked from both thoracic aorta and mesenteric arteries by the two modes of stimulation. Cinnarizine blocked the Ca-evoked contraction of the depolarized vessels but was less effective against the noradrenaline-induced contraction of the mesenteric arteries and even failed to antagonize the response of the thoracic aorta to noradrenaline. In Ca-free medium noradrenaline (10-5 M) evoked a fast non-sustained contraction. After readmission of CaCl2 a slow sustained contraction developed. In mesenteric arteries exposed to noradrenaline, cinnarizine selectively blocked the Ca0 dependent response while papaverine inhibited the initial fast response more than the Ca0 dependent one. These results suggest that cinnarizine and papaverine antagonize vascular contraction by different mechanisms. Cinnarizine seems to act by reducing membrane permeability to extracellular calcium. Papaverine inhibits the contraction by a main action on intracellular sequestration of activator calcium and to a lesser degree by an action similar to that of cinnarizine.