Leukotrienes mediate tracheal hyperresponsiveness after nitric oxide synthesis inhibition

Preincubation of guinea pig tracheas with the nitric oxide synthase inhibitor, N ω-nitro- l-arginine methyl ester (L-NAME, 120 μM) 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-benoquinone) 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-4 H-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.