LEUKOTRIENES MEDIATE TRACHEAL HYPERRESPONSIVENESS AFTER NITRIC-OXIDE SYNTHESIS INHIBITION

Preincubation of guinea pig tracheas with the nitric oxide synthase in hibitor, N-omega-nitro-L-arginine methyl ester (L-NAME, 120 mu M) resu lted in a significant upward shift of the histamine concentration-resp onse curve with a concomitant inhibition of prostaglandin E(2) product ion. Preincubation of the preparations with a 5-lipoxygenase inhibitor (AA-861, xy-5,10-dodecadiynyl)-3,5,6-trimethyl-p-benzoquine or a leuk otriene C-4,D-4,E(4) receptor antagonist (FPL 55712, sodium -{3-(4-ace tyl-3-hydroxy-2-propylphenoxy)-2-hydroxy oxy}-4-oxo-8-propyl-4H-1-benz opyran-2-carboxylate) totally blocked the L-NAME-induced tracheal hype rresponsiveness. A shift from cyclo-oxygenase to lipoxygenase products , in particular leukotrienes, is likely to be responsible for the L-NA ME-induced tracheal hyperresponsiveness.