We hypothesized that tachykinins, thromboxane A2 (TXA2), and nitric oxide (NO) contribute to the pathogenesis of airway inflammation and hyperresponsiveness. A specific tachykinin antagonist, FK224, inhibited smoke-induced plasma extravasation, airway responsiveness, and neutrophil influx in bronchoalveolar lavage (BAL) fluid. TXB2 levels in BAL fluid increased after smoke-exposure and the increase was significantly inhibited by FK224. A TXA2 synthase inhibitor, OKY-046, inhibited airway hyperresponsiveness, but had no effect on plasma extravasation or neutrophil influx. The depletion of tachykinins by capsaicin prevented bronchiolar wall edema, airway hyperresponsiveness, and neutrophil influx in BAL fluid caused by ozone exposure. NO synthase inhibitors had no effect on airway inflammation or hyperresponsiveness immediately after ozone, but significantly inhibited those changes 5 h after ozone. These results suggest that immediately after smoke or ozone exposure, tachykinins play an important role in airway inflammation and hyperresponsiveness, TXA2 (possibly released from inflammatory cells), but not plasma extravasation per se, is responsible for the development of airway hyperresponsiveness. On the other had, NO may modulate persistent airway inflammation and hyperresponsiveness after exposure to ozone.
|ジャーナル||Japanese Journal of Thoracic Diseases|
|出版ステータス||出版済み - 1997|
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