Journal of Applied Physiology
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J Appl Physiol 85: 442-450, 1998;
8750-7587/98 $5.00
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Vol. 85, Issue 2, 442-450, August 1998

Role of tachykinins in airway responses to ozone in rats

Toru Takebayashi1, Joseph Abraham1, G. G. Krishna Murthy1, Craig Lilly2, Ian Rodger3, and Stephanie A. Shore1

1 Physiology Program, Harvard School of Public Health, and 2 Pulmonary Division, Brigham and Women's Hospital, Boston, Massachusetts 02115; and 3 Merck Frosst Center for Therapeutic Research, Kirkland, Quebec, Canada H9H 3L1

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 (VE) 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 VE 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 VE.

airway responsiveness; bronchoconstriction; methacholine; C fibers; ventilation; CP-99994; SR-48968; bronchoalveolar lavage; tidal volume; breathing frequency


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