TY - JOUR
T1 - The effects of a specific tachykinin receptor antagonist FK-224 on ozone-induced airway hyperresponsiveness and inflammation
AU - Aizawa, H.
AU - Koto, H.
AU - Nakano, H.
AU - Inoue, H.
AU - Matsumoto, K.
AU - Takata, S.
AU - Shigyo, M.
AU - Hara, N.
PY - 1997/1/1
Y1 - 1997/1/1
N2 - We have demonstrated previously that tachykinin depletion by capsaicin prevented the ozone-induced airway hyperresponsiveness and the bronchial wall oedema in guinea pigs. To further clarify the role of neurogenic inflammation in ozone-induced airway hyperresponsiveness, we investigated the effects of a specific tachykinin receptor antagonist (FK-224) in guinea pigs. Animals were anaesthetized, tracheostomized and mechanically ventilated. Total pulmonary resistance (R(L)) was calculated from transpulmonary pressure and box flow in a plethysmograph. Airway responsiveness was assessed by determining the provocative concentration of histamine aerosol that increased R(L) to twice the baseline value (PC200). Animals were injected with either FK-224 (10 mg/kg, dissolved in 0.2 mL/kg DMSO) or vehicle (0.2 mL/kg DMSO) intravenously, then pre-ozone PC200 was determined. Following this measurement, animals were exposed to 3 ppm ozone for 60 min. Immediately after exposure, the histamine dose response curve was evaluated again. Bronchoalveolar lavage (BAL) was performed in animals treated with FK-224 or vehicle. In animals treated with vehicle, ozone exposure caused significant decrease in PC200 and moderate increase in neutrophils in BAL fluid. FK- 224 pre-treatment significantly inhibited ozone-induced hyperresponsiveness. Neutrophils in BAL fluid did not significantly increase after ozone exposure in animals treated with FK-224. By contrast, the degree of epithelial desquamation did not differ significantly between the two groups. We conclude that neurogenic inflammation caused by tachykinin release may be responsible for ozone-induced bronchial hyperresponsiveness, and that tachykinins may play a role in the initiation of airway inflammation.
AB - We have demonstrated previously that tachykinin depletion by capsaicin prevented the ozone-induced airway hyperresponsiveness and the bronchial wall oedema in guinea pigs. To further clarify the role of neurogenic inflammation in ozone-induced airway hyperresponsiveness, we investigated the effects of a specific tachykinin receptor antagonist (FK-224) in guinea pigs. Animals were anaesthetized, tracheostomized and mechanically ventilated. Total pulmonary resistance (R(L)) was calculated from transpulmonary pressure and box flow in a plethysmograph. Airway responsiveness was assessed by determining the provocative concentration of histamine aerosol that increased R(L) to twice the baseline value (PC200). Animals were injected with either FK-224 (10 mg/kg, dissolved in 0.2 mL/kg DMSO) or vehicle (0.2 mL/kg DMSO) intravenously, then pre-ozone PC200 was determined. Following this measurement, animals were exposed to 3 ppm ozone for 60 min. Immediately after exposure, the histamine dose response curve was evaluated again. Bronchoalveolar lavage (BAL) was performed in animals treated with FK-224 or vehicle. In animals treated with vehicle, ozone exposure caused significant decrease in PC200 and moderate increase in neutrophils in BAL fluid. FK- 224 pre-treatment significantly inhibited ozone-induced hyperresponsiveness. Neutrophils in BAL fluid did not significantly increase after ozone exposure in animals treated with FK-224. By contrast, the degree of epithelial desquamation did not differ significantly between the two groups. We conclude that neurogenic inflammation caused by tachykinin release may be responsible for ozone-induced bronchial hyperresponsiveness, and that tachykinins may play a role in the initiation of airway inflammation.
UR - http://www.scopus.com/inward/record.url?scp=0031410274&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031410274&partnerID=8YFLogxK
U2 - 10.1111/j.1440-1843.1997.tb00087.x
DO - 10.1111/j.1440-1843.1997.tb00087.x
M3 - Article
C2 - 9525295
AN - SCOPUS:0031410274
SN - 1323-7799
VL - 2
SP - 261
EP - 265
JO - Respirology
JF - Respirology
IS - 4
ER -