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

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 aM) 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 (ej.ps) and repetitive stimulation produced a facilitation of ej.ps in both tissues. Pinacidil (over 1 piM) reduced the amplitude and the decay time of ej.ps to a consistently greater extent in the rabbit mesenteric artery than in the guinea-pig. However, the facilitation process of ej.ps was not modified following application of pinacidil (1 pM). The pinacidil-induced inhibition of ej.ps was prevented by pretreatment with glibenclamide.4 Pinacidil (30pM) marginally increased the overflows of NA and its metabolite, 3,4-dihydroxyphenylglycol (DOPEG) released following repetitive perivascular nerve stimulations. 5 Pinacidil (10pM) partly inhibited the voltage-dependent Ca channel, as estimated from the recovery process following removal of pinacidil, of action potentials evoked on ej.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.

Effects of pinacidil on contractile proteins in high K+‐treated intact, and in β‐escin‐treated skinned smooth muscle of the rabbit mesenteric artery

“…Glibenclamide is a selective inhibitor of this channel in vascular smooth muscles (Standen et al, 1989). In the present experiments, however, we observed that pinacidil (10pM) (Nakashima et al, 1990) and glibenclamide did not affect the inhibitory action of pinacidil. The extent of the contraction induced by high K+ is thought to be closely related to the [Ca21]i (Morgan & Morgan, 1984), yet 10,uM pinacidil inhibited the contraction without any decrease in [Ca2 +]; .…”

Pre-junctional Stimulatory and Post-junctional Inhibitory Effects of Pinacidil in the Isolated Main Pulmonary Artery of the Rabbit under Different Experimental Conditions

“…A similar, marginal permeability and a decrease of Cl − -permeability, pre-synaptic stimulatory effect was reported by Nederwhereas no change of Na + -permeability was obgaard 20 in rabbit pulmonary artery, by Nakashima served. 6 In line with these observations, it was shown and co-authors 21 in guinea-pig and rabbit mesenteric that pinacidil inhibits the NA-induced contraction of artery and by Fabiani & Story 15 in rat mesenteric rabbit mesenteric artery. 5 The two different Ca extent of inhibition of NA-induced contraction by This may explain the marginal stimulatory action of pinacidil ( Fig.…”

The Effect of Potassium Channel Opener Pinacidil on the Non‐Pregnant Rat Uterus

“…Indeed, it has been reported that in airway smooth muscle preparations [26], in the rat urinary bladder [27], in the rat vas deferens [28] and in the rabbit portal vein [11], pinacidil inhibits release of neurotransmitters. In contrast, in the guinea‐pig and rabbit mesenteric arteries, pinacidil and cromakalim had no effect on presynaptic neurotransmitter release [29,30]. However, these observations need further evaluation.…”