ROLE OF TACHYKININS IN OZONE-INDUCED ACUTE LUNG INJURY IN GUINEA-PIGS

To examine the hypothesis that the acute reversible changes caused by ozone (O3) exposure are mediated by tachykinin release, guinea pigs we re depleted of tachykinins by use of repeated capsaicin (CAP) injectio ns before O3 exposure in an attempt to prevent O3-induced functional c hanges. Unexpectedly, CAP pretreatment caused divergent results in the functional responses to O3. Ventilatory measurements obtained from CA P-pretreated O3-exposed (CAP-O3) animals were exacerbated rather than diminished compared with the effects of O3 alone. Similarly, lavage fl uid protein accumulation was enhanced in the CAP-O3 group compared wit h the O3-exposed group. In better agreement with our initial hypothesi s, the CAP-O3 group was less responsive than the O3-exposed animals to histamine aerosol challenge. Additionally, Evans blue dye accumulatio n, a hallmark of tachykinin release, was increased in O3-exposed anima ls and was partially blocked in the CAP-O3 group. These data suggest t hat tachykinin-containing sensory fibers are unlikely to mediate the a cute effects of O3 exposure on tidal breathing and lavage fluid protei n accumulation but may play a role in causing post-O3 airway hyperreac tivity and protein extravasation into the trachea.