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 microelectrode and isometric tension recording methods for intact cells. The effects of nifedipine on the mechanical response on saponin-treated skinned muscles were also studied. Nifedipine inhibited the Ca spike evoked by outward current pulses in the presence of tetraethylammonium and that by perivascular nerve stimulation without affecting the amplitude of excitatory junction potentials. Nifedipine (less than 3 X 10(-7) M) modified neither the amplitude of excitatory junction potentials nor the facilitation process. This drug inhibited the contractions evoked by direct muscle stimulation under conditions of treatment with guanethidine and tetrodotoxin, excess concentrations of [ K ]O, exogenously applied norepinephrine (NE) and perivascular nerve stimulation. The K-induced contraction was markedly inhibited by nifedipine (greater than 3 X 10(-9) M) and the potency of the inhibitory action of nifedipine appeared in the following order: direct muscle stimulation greater than perivascular nerve stimulation greater than exogenously applied NE. Nifedipine inhibited the NE-induced oscillatory contractions more than the NE-induced tonic and phasic contractions. In Na-free solution, the tissue generated a small tonic contraction after 20 to 30 min superfusion. This contraction ceased with application of nifedipine. In the saponin-treated skinned muscles (50 micrograms/ml for 20 min), Ca accumulation into and Ca release from the store sites, as well as the contractile proteins including calmodulin, were not affected by nifedipine (1 X 10(-7) M). These results indicate that nifedipine only acts 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.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004558:Electric Stimulation; D005260:Female; D008297:Male; D008638:Mesenteric Arteries / Q000294:innervation; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D011817:Rabbits
D011725:Pyridines; D009543:Nifedipine; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine