INVOLVEMENT OF TACHYKININ RECEPTORS (NK1 AND NK2) IN SODIUM METABISULFITE-INDUCED AIRWAY EFFECTS

We have investigated the effects of CP-96,345 and SR-48968, new nonpep tide (neurokinin) NK1 and NK2 receptor antagonists, respectively, agai nst bronchoconstriction and airway microvascular leakage induced by in haled sodium metabisulfite (MBS) in anesthetized guinea pigs. Lung res istance (RL) was measured for 6 min after challenge, followed by measu rement of extravasation of Evans blue dye into airway tissues, used as an index of airway microvascular leakage. MBS (80 mM, 30 breaths) cau sed a significant increase in RL and leakage of dye at all airway leve ls. CP-96,345 (2 mg/kg, intravenous) but not SR-48968 (1.5 mg/kg, intr avenous) significantly inhibited the leakage of dye at all airway leve ls except for trachea. Each antagonist inhibited significantly the max imal increase in RL. The combination had a significant additive effect against the bronchoconstriction, when compared with SR-48968 alone, a nd significantly inhibited the leakage of dye at the same airway level s as CP-96,345. We conclude that bronchoconstriction induced by inhale d MBS is, at least partly, mediated by activation of both NK1 and NK2 receptors, and the airway microvascular leakage by NK1 receptor stimul ation alone.