MECHANISM OF COOLING-INDUCED RELAXATION IN THE ISOLATED GUINEA-PIG TRACHEA

In this study, we explored the possible mechanism of cooling-induced r elaxation of the isolated guinea-pig trachea. A rapid cooling (-4 degr ees C/min) from 37+/-0.5 degrees C to 25+/-0.5 degrees C induced a tra nsient and small contraction followed by a sustained cooling-relaxatio n. This relaxation was not blocked by propranolol or tetrodotoxin. Var ious concentrations of four contractile agonists (histamine, carbachol , 5-HT and ryanodine) all enhanced cooling-relaxation in a concentrati on-dependent manner which correlated well with their increase in the d eveloped muscular tension, suggesting an inherent counterbalance betwe en cooling-relaxation and the bronchoconstriction. Treating with eithe r indomethacin or nordihydroguaiaretic acid (NDGA) did not affect the contractile properties of histamine, carbachol and 5-HT except ryanodi ne, but reversed cooling-relaxation into sustained cooling-contraction . Indomethacin partially inhibited but NDGA abolished cooling-relaxati on induced by ryanodine. Moreover, ryanodine, but not the other three contractile agonists, could antagonize indomethacin in inducing coolin g-contractions by various agonists. From above findings, we can conclu de that eicosanoids including prostaglandins particularly leukotrienes , which would be produced by the elevated Ca2+-release from the ryanod ine sensitive Ca2+-store, play prominent roles in inducing cooling-rel axation.