Effects of nifedipine on smooth muscle cells of the rabbit mesenteric artery.

The effects of nifedipine on electrical and mechanical responses of smooth muscle cells of the rabbit mesenteric artery were investigated using the microelectrode and isometric tension recording methods for intact cells and saponin-treated skinned muscles. Nifedipine inhibited the Ca-spike evoked by outward current pulses in the presence of tetraethylammonium (TEA) and that by perivascular nerve stimulation without affecting the amplitude of excitatory junction potentials (EJPs). Nifedipine(<3×10−7M) modified neither the amplitude of EJPs nor the facilitation process. This drug inhibited the contraction evoked by direct muscle stimulation under conditions of treatment with guanethidine and tetrodotoxin(TTX), excess concentrations of [K]o exogenously applied norepinephrine(NE) and perivascular nerve stimulation. The K-induced contraction was markedly inhibited by nifedipine (>3×10−9M), and the potencies of inhibitory action of nifedipine appeared in the following order: direct muscle stimulation>perivascular nerve stimulation>exoge-nously applied NE. Nifedipine inhibited the NE-induced oscillatory contractions more than the NE-induced tonic and phasic contractions. In the Na-free solution, the tissue generated a small tonic contraction after 20-30 min superfusion. This contraction ceased with application of nifedipine. In the saponin treated muscles (50μg/ml for 20min), Ca accumulation into and Ca release from the store sites, as well as the contractile proteins including calmodulin, were not affected by nifedipine (1×10−7M). These results indicate that nifedipine acts only on the myoplasmic membrane of smooth muscles of the mesenteric artery. The nifedipine-induced relaxation appears to be due to inhibition of the voltage dependent Ca channel.