The effect of mixed inhibitors of cyclo-oxygenase and lipoxygenase on the indomethacin-induced hyper-reactivity in the isolated trachea of the pig.

1 Indomethacin enhances muscle contraction to histamine in the pig isolated trachea. The effect of three cyclo-oxygenase/lipoxygenase inhibitors on these potentiated histamine-induced responses was examined. 2 At the higher concentrations BW 755c (113-226 microM), 5, 8, 11, 14-eicosatetraynoic acid (ETYA, 10-100 microM) and phenidone (5-500 microM) abolished the effect of indomethacin on tracheal contractions to histamine (100 microM). 3 Each of the three inhibitors also reduced the slope of the histamine concentration-response curve obtained in the presence of indomethacin. However, the sensitivity (pD2) of the smooth muscle to histamine was not affected by BW 755c, ETYA or phenidone. 4 The results provide further support for a lipoxygenase-dependent component of indomethacin-induced hyper-reactivity in the pig trachea.