AN IMPORTANT ROLE OF TACHYKININS IN OZONE-INDUCED AIRWAY HYPERRESPONSIVENESS

We investigated the role of tachykinins in ozone-induced airway hyperr esponsiveness (AHR) in guinea pigs. Airway responsiveness was assessed by determining the provocative concentration (PC200) of a histamine a erosol. Ozone exposure (3.0 ppm for 2 h) caused significant AHR. For v ehicle-pretreated animals, the geometric mean pre- and post-ozone PC20 0 values were 0.87 mg/ml (GSEM 1.33) and 0.11 mg/ml (GSEM 1.17), respe ctively. Tachykinin depletion by capsaicin (50 mg/kg) prevented this A HR, whereas it did not alter pre-ozone airway responsiveness. The PC20 0 was 0.36 mg/kg (GSEM 1.64) before ozone and 0.24 mg/kg (GSEM 1.72) a fter ozone for this group. Ozone also caused a significant increase in neutrophils in bronchoalveolar lavage fluid (BALF) compared with BALF from a normal control group (1.71 +/- 0.69 versus 0.07 +/- 0.02 x 10( 5)/ml, respectively). Capsaicin pretreatment attenuated this neutrophi l influx(0.23 +/- 0.16 x 10(5)/ml). Morphometric assessment revealed e dema of the bronchiolar wall after ozone exposure, which was not obser ved in the capsaicin group. BAL and morphometry revealed that the degr ee of ozone-induced epithelial desquamation was similar in both groups . These results suggest that tachykinins may be responsible for ozone- induced AHR, possibly via neurogenic inflammation.