Chlorzoxazone inhibits contraction of rat thoracic aorta.
Chlorzoxazone has been reported to activate the intermediate-conductance, Ca(2+)-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 muM noradrenaline in an endothelium independent manner. Preincubation with chlorzoxazone also antagonized the contraction induced by 1 microM 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 microM paxilline, but not by 2 microM clotrimazole. Chlorzoxazone relaxed the 4-aminopyridine-induced contraction. The pattern of chlorzoxazone-induced relaxation was different from that of verapamil, the L-type Ca(2+) 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, Ca(2+)-activated K(+) channels.
Dong
De-Li
DL
Department of Pharmacology, Harbin Medical University, Bio-pharmaceutical Key Laboratory of Heilongjiang Province, Baojian Road 157, Harbin 150086, Heilongjiang Province, PR China. delidong2004@yahoo.com.cn
Luan
Yan
Y
Feng
Tie-Ming
TM
Fan
Chang-Long
CL
Yue
Peng
P
Sun
Zhi-Jie
ZJ
Gu
Rui-Min
RM
Yang
Bao-Feng
BF
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D002753:Chlorzoxazone / Q000097:blood / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology; D066298:In Vitro Techniques; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000187:drug effects / Q000502:physiology; D008297:Male; D009125:Muscle Relaxants, Central / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology
D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; D009125:Muscle Relaxants, Central; D000431:Ethanol; D011189:Potassium Chloride; D014700:Verapamil; D002753:Chlorzoxazone; D009638:Norepinephrine