4-Aminopyridine attenuates endothelium-derived hyperpolarizing factor-induced hyperpolarization and relaxation of rat mesenteric small arteries (part 7)
4-AP is known to block delayed rectifier potassium currents. Although in SMC of cerebral arteries 4-AP was shown to inhibit ATP-sensitive potassium currents as well, in our experiments the hyperpolarizing vasodilator cromacalim (10-8 to 10-6 M) induced relaxation of mesenteric arteries, which was blocked by glibenclamide (10-6 M), an inhibitor of ATP-sensitive potassium channels, but not by 4-AP (5 mM) (data not shown). Moreover, in SMC isolated from the mesenteric arteries used in our experiments outward currents contained the ATP-sensitive voltage-independent component, which is potentiated by cromacalim and inhibited by glibenclamide but not by 4-AP . These results suggest that in rat mesenteric artery SMC, 4-AP does not affect ATP-sensitive potassium channels.
In the presence of LNNA and indomethacin, 4-AP completely blocked carbachol-induced hyperpolarization of SMC and relaxation of noradrenaline-preconstricted vessels. Exposure to LNNA and indomethacin 1 h before application of carbachol and the presence of these blockers throughout the experiments imply that nitric oxide synthase and cyclo-oxygenase were inactive. Under these conditions only EDHF could produce hyperpolarization of SMC and subsequent relaxation of intact vessels upon the application of carbachol. The lack of dramatic changes in SMC membrane potential and in resting vessel wall tension in response to exposure to LNNA and indomethacin, as well as to 4-AP in concentrations capable of blocking carbachol-induced nitric oxide- and prostanoid-resistant SMC hyperpolarization and vessel relaxation, implies that basal release of nitric oxide, prostanoids and EDHF from endothelium of rat mesenteric arteries is not substantial. However, further investigation is required to assess more precisely the ratio of basal release of endothelium-derived factors. You can soon shop with a nice pharmacy offering cheap ventolin inhalers to benefit more.