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

Wu, Zhong-Xin, Robert F. Morton, and Lu-Yuan Lee. Roleof tachykinins in ozone-induced airway hyperresponsiveness to cigarettesmoke in guinea pigs. J. Appl.Physiol. 83(3): 958-965, 1997.Acute exposure to ozone(O₃) induces airwayhyperresponsiveness to various inhaled bronchoactive substances.Inhalation of cigarette smoke, a common inhaled irritant in humans, isknown to evoke a transient bronchoconstrictive effect. To examinewhether O₃ increases airwayresponsiveness to cigarette smoke, effects of smoke inhalationchallenge on total pulmonary resistance(RL) and dynamic lungcompliance (Cdyn) were compared before and after exposure toO₃ (1.5 ppm, 1 h) in anesthetizedguinea pigs. Before O₃ exposure,inhalation of two breaths of cigarette smoke (7 ml) at a lowconcentration (33%) induced a mild and reproduciblebronchoconstriction that slowly developed and reached its peak(RL = 67 ± 19%, Cdyn = 29 ± 6%) after a delay of >1 min. After exposure toO₃ the same cigarette smokeinhalation challenge evoked an intense bronchoconstriction thatoccurred more rapidly, reaching its peak(RL = 620 ± 224%, Cdyn = 35 ± 7%) within 20 s, and was sustained for >2min. By contrast, sham exposure to room air did not alter thebronchomotor response to cigarette smoke challenge. Pretreatment withCP-99994 and SR-48968, the selective antagonists of neurokinin type 1 and 2 receptors, respectively, completely blocked the enhancedresponses of RL and Cdyn tocigarette smoke challenge induced byO₃. These results show thatO₃ exposure induces airwayhyperresponsiveness to inhaled cigarette smoke and that the enhancedresponses result primarily from the bronchoconstrictive effect ofendogenous tachykinins.