LEUKOTRIENES MEDIATE TRACHEAL HYPERRESPONSIVENESS AFTER NITRIC-OXIDE SYNTHESIS INHIBITION

Preincubation of guinea pig tracheas with the nitric oxide synthase inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME, 120 mu M) resulted in a significant upward shift of the histamine concentration-response curve with a concomitant inhibition of prostaglandin E(2) production. Preincubation of the preparations with a 5-lipoxygenase inhibitor (AA-861, 2-(12-hydroxy-5,10-dodecadiynyl)-3,5,6-trimethyl-p-benzoquine or a leukotriene C-4,D-4,E(4) receptor antagonist (FPL 55712, sodium 7-{3-(4-acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxy propoxy}-4-oxo-8-propyl-4H-1-benzopyran-2-carboxylate) totally blocked the L-NAME-induced tracheal hyperresponsiveness. A shift from cyclo-oxygenase to lipoxygenase products, in particular leukotrienes, is likely to be responsible for the L-NAME-induced tracheal hyperresponsiveness.