Chlorzoxazone inhibits contraction of rat thoracic aorta

Chlorzoxazone has been reported to activate the intermediate-conductance, Ca2+-activated K+ channels in aortic endothelial cells and to relax the artery. The aim of the present study was to characterize the chlorzoxazone-induced relaxation of rat thoracic artery. Chlorzoxazone did not affect the tension of the thoracic artery rings at rest, but relaxed the precontraction induced by 1 mu M noradrenaline in an endothelium independent manner. Preincubation with chlorzoxazone also antagonized the contraction induced by 1 mu M noradrenaline or 25 mM KCl. The chlorzoxazone-induced relaxation of the thoracic artery pre-contracted by noradrenaline was suppressed by 5 mM tetraethylammonium, 75 MM ethanol and 2 mu M paxilline, but not by 2 mu M clotrimazole. Chlorzoxazone relaxed the 4-aminopyridine-induced contraction. The pattern of chlorzoxazone-induced relaxation was different from that of verapamil, the L-type Ca2+ channel blocker. The inhibition of the noradrenaline-induced contraction by chlorzoxazone was attenuated when chlorzoxazone treatment was prolonged to 4 h. No difference in the contraction-relaxation was found between the artery rings from normal rats and those from rats that received 100 mg/kg chlorzoxazone for 7 days. We conclude that chlorzoxazone abolishes the contraction of rat thoracic artery induced by noradrenaline and that the effect of chlorzoxazone is endothelium independent and also not mediated by intermediate-conductance, Ca2+-activated K+ channels. (c) 2006 Elsevier B.V. All rights reserved.