An important role of tachykinins in ozone-induced airway hyperresponsiveness.
We investigated the role of tachykinins in ozone-induced airway hyperresponsiveness (AHR) in guinea pigs. Airway responsiveness was assessed by determining the provocative concentration (PC200) of a histamine aerosol. Ozone exposure (3.0 ppm for 2 h) caused significant AHR. For vehicle-pretreated animals, the geometric mean pre- and post-ozone PC200 values were 0.87 mg/ml (GSEM 1.33) and 0.11 mg/ml (GSEM 1.17), respectively. Tachykinin depletion by capsaicin (50 mg/kg) prevented this AHR, whereas it did not alter pre-ozone airway responsiveness. The PC200 was 0.36 mg/kg (GSEM 1.64) before ozone and 0.24 mg/kg (GSEM 1.72) after 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 neutrophil influx (0.23 +/- 0.16 x 10(5)/ml). Morphometric assessment revealed edema of the bronchiolar wall after ozone exposure, which was not observed in the capsaicin group. BAL and morphometry revealed that the degree 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.
Koto
H
H
Research Institute for Diseases of the Chest, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Aizawa
H
H
Takata
S
S
Inoue
H
H
Hara
N
N
D000818:Animals; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002211:Capsaicin / Q000494:pharmacology; D006168:Guinea Pigs; D006632:Histamine; D009504:Neutrophils; D010126:Ozone / Q000009:adverse effects*; D011292:Premedication; D015320:Tachykinins / Q000187:drug effects / Q000502:physiology*
D015320:Tachykinins; D010126:Ozone; D006632:Histamine; D002211:Capsaicin