Pinacidil inhibits neuromuscular transmission indirectly in the guinea-pig and rabbit mesenteric arteries

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Abstract
1 Effects of pinacidil were investigated on neuromuscular transmission in smooth muscle tissues of the rabbit and guinea-pig mesenteric arteries by both electrophysiological procedures and a bioassay of noradrenaline (NA) outflows. 2 Pinacidil (over 1 μm) hyperpolarized smooth muscle cell membranes in both tissues, in a concentration dependent manner. Pinacidil hyperpolarized and increased the ionic conductance of smooth muscle membrane more markedly in the rabbit mesenteric artery than in the guinea-pig. The hyperpolarization induced by pinacidil occurred in the presence or absence of endothelial cells and was blocked by glibenclamide. 3 Perivascular adrenergic nerve stimulation produced excitatory junction potentials (e.j.ps) and repetitive stimulation produced a facilitation of e.j.ps in both tissues. Pinacidil (over 1 μm) reduced the amplitude and the decay time of e.j.ps to a consistently greater extent in the rabbit mesenteric artery than in the guinea-pig. However, the facilitation process of e.j.ps was not modified following application of pinacidil (1 μm). The pinacidil-induced inhibition of e.j.ps was prevented by pretreatment with glibenclamide. 4 Pinacidil (30 μm) marginally increased the overflows of NA and its metabolite, 3,4-dihydroxyphenylglycol (DOPEG) released following repetitive perivascular nerve stimulations. 5 Pinacidil (10 μm) partly inhibited the voltage-dependent Ca channel, as estimated from the recovery process following removal of pinacidil, of action potentials evoked on e.j.ps. 6 It is concluded that pinacidil increases ionic conductance and hyperpolarizes smooth muscle cell membranes of the guinea-pig and rabbit mesenteric arteries and as a consequence, inhibits the neuromuscular transmission process occurring on adrenergic nerve stimulation with no reduction in the amount of released transmitter.