Involvement of tachykinins in ozone-induced airway hyperresponsiveness to cigarette smoke in guinea pigs

Inhalation of cigarette smoke induces a biphasic bronchoconstriction; the early phase is induced by a combination of cholinergic reflex and tachykinins, while the late phase involves a release of prostanoids (JAP 78:2260, 1995). To examine whether the bronchomotor response to cigarette smoke is altered by O₃, effects of smoke inhalation challenge on Rj. and C_dyn were compared before and after exposure to O3 (1.5 ppm, I hr) in anesthetized guinea pigs. Prior to O₃ exposure, inhalation of two breaths of cigarette smoke (UK. 2R1 cigarette, 7ml) at a low concentration (33%) induced only a mild late-phase response that reached its peak after - 50 breaths (AR_L=67±19%, and AC_dyn =-29±6%); there was no detectable early phase. After exposure to Oî, the baseline R_L was not significantly different from control, but the same smoke inhalation challenge evoked an intense early-phase response within 10-15 breaths (ARL=620±224%, and AC_dyn=-35±7%); the late phase was not significantly different from control. By contrast, the bronchomotor response to smoke inhalation challenge was not altered after exposure to room air. Pretreatment with CP-99994 and SR-48968, the antagonists of neurokinin-1 and neurokinin-2 receptors, respectively, completely blocked the enhanced bronchomotor response to smoke inhalation challenge induced by O3. These results indicate that O3 exposure induces airway hyperresponsiveness to inhaled cigarette smoke, and the enhanced response results primarily from the bronchoconstrictive effect of endogenously released tachykinins. (Supported by NIH grants 40369. 52172 and KTRB grant 5-41066).