Effects of Ca-antagonists on neuromuscular transmission in the rabbit ear artery.
1. The effects of three Ca-antagonists: diltiazem, nicardipine and flunarizine have been studied on excitatory junction potentials (e.j.p.s), force development and efflux of transmitter during stimulation of perivascular nerves in the rabbit ear artery. 2. Stimulation of these perivascular nerves produces excitatory junction potentials and repetitive stimulation causes facilitation. Increasing the frequency or the number of stimuli initiates an action potential and a large contraction. Both phenomena are completely suppressed by 3 X 10(-7) M TTX. 3. Ca-antagonists at 10(-5) M do not affect the resting membrane potential, but flunarizine and nicardipine at concentrations exceeding 10(-5) M reduce the amplitude of e.j.p.s and of the action potentials and also the concomitant contraction induced by nerve stimulation. Diltiazem at concentrations below 3 X 10(-5) M has no effect on e.j.p.s and action potentials while at 10(-4) M, it largely suppresses e.j.p.s, spikes and contraction. This inhibitory effect of the Ca-antagonists increases with prolonged exposure. 4. All these Ca-antagonists induce an increased release of 3H-DOPEG from the nerve terminals, but in our experiments in vitro they do not reduce the efflux of 3H-noradrenaline induced by nerve stimulation. 5. The results indicate that Ca-antagonists might affect the excitation-contraction coupling in vivo by inhibiting the Ca influx activated by endogenous noradrenaline. They do not exert an acute effect on the noradrenaline release induced by stimulation. The increased DOPEG release by Ca-antagonists remains unexplained.
D000818:Animals; D001158:Arteries / Q000294:innervation*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004423:Ear / Q000098:blood supply*; D004558:Electric Stimulation; D005260:Female; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009411:Nerve Endings / Q000378:metabolism; D009469:Neuromuscular Junction / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D011817:Rabbits; D009435:Synaptic Transmission / Q000187:drug effects*
D002121:Calcium Channel Blockers; D009638:Norepinephrine