Role of tachykinins in airway responses to ozone in rats

Previous studies that used neonatal capsaicin (Cap) treatment to ablate C fibers indicate that C fibers act to inhibit lung damage and airway hyperresponsiveness after ozone (O₃) exposure in rats. The purpose of this study was to determine 1) the role of tachykinins in these protective effects and 2) whether differences in minute ventilation (V̇E) during O₃ exposure might account for the effect of Cap. In the first study, male Sprague-Dawley rats were exposed to 1 part/million O₃ or air for 3 h. Four hours later, a bronchoalveolar lavage (BAL) was performed or airway responsiveness was measured. Rats were treated with CP-99994 and SR-48968, selective neurokinin- 1-and -2-receptor antagonists, respectively, or with vehicle (Veh). O₃ caused an increase in the number of neutrophils recovered from BAL fluid in both the Veh-treated and tachykinin-receptor antagonist (TKRA)-treated rats, but the number of neutrophils was approximately twofold greater in the TKRA- treated rats. In contrast, TKRA treatment had no effect on baseline pulmonary mechanics or airway responsiveness. After O₃ exposure, the number of neutrophils in BAL fluid was also greater in Cap- than in Veh-treated rats. O₃ reduced V̇E in both Veh- and Cap-treated rats, but the response was greater (reduction of 44.7 ± 3.7 vs. 27.8 ± 6.8%) and occurred earlier (10 vs. 70 min) in Cap- than in Veh-treated rats (P < 0.02). These results suggest that tachykinins mediate protective effects of C fibers against O₃- induced lung inflammation. The results also indicate that the more pronounced effect of O₃ on BAL neutrophils in Cap-treated rats is not the result of a greater inhaled dose of O₃ resulting from greater V̇E.