Effect of tranilast on endothelin-induced bronchoconstriction in guinea pigs.
Tranilast, an anti-asthmatic drug with anti-allergic properties, inhibited endothelin (ET)-induced asthmatic like respiratory obstruction in guinea pigs when administered orally at 200 mg/kg 1 h prior to the intravenous injection of ET. ET also caused a bronchoconstriction detected as an increase in inflation pressure in Konzett-Rössler apparatus. Tranilast (200 mg/kg, p.o. 1 h before ET) inhibited ET-induced increased inflation pressure. ET-induced bronchoconstriction detected as an increase in inflation pressure was clearly inhibited by the administration of indomethacin (used as a reference drug) at doses of 1 and 5 mg/kg 30 min prior to onset of the reaction. In addition to the above in vivo experiments, tranilast at concentrations between 10(-5) and 10(-4) g/ml inhibited ET-induced contraction of isolated guinea pig tracheal muscle, whereas indomethacin did not affect this in vitro response. In order to elucidate the inhibitory mechanism of tranilast on ET-induced bronchoconstriction, the effects in Ca(2+)-free medium and on ET-induced histamine and prostaglandin F2 alpha release from tracheal muscle were investigated. Consequently, tranilast did not affect ET-induced contraction of guinea pig tracheal muscle in Ca(2+)-free Tyrode's solution and ET induced neither histamine nor PGF2 alpha release. These results suggest that tranilast inhibits ET-induced bronchoconstriction by inhibiting the ET-induced calcium influx into tracheal muscle.
Nagai
H
H
Department of Pharmacology, Gifu Pharmaceutical University, Japan.
Suda
H
H
Kitagaki
K
K
Koda
A
A
D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects*; D015237:Dinoprost / Q000378:metabolism; D016232:Endothelins / Q000494:pharmacology*; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D014132:Trachea / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D016232:Endothelins; D006634:Histamine H1 Antagonists; D062367:ortho-Aminobenzoates; D015237:Dinoprost; C012293:tranilast