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The effects of a specific tachykinin receptor antagonist FK‐224 on ozone‐induced airway hyperresponsiveness and inflammation
Author(s) -
AIZAWA H,
KOTO H,
NAKANO H,
INOUE H,
MATSUMOTO K,
TAKATA S,
SHIGYO M,
HARA N
Publication year - 1997
Publication title -
respirology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 85
eISSN - 1440-1843
pISSN - 1323-7799
DOI - 10.1111/j.1440-1843.1997.tb00087.x
Subject(s) - medicine , bronchoalveolar lavage , histamine , tachykinin receptor , bronchial hyperresponsiveness , pharmacology , immunology , antagonist , endocrinology , receptor , lung , respiratory disease , substance p , neuropeptide
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 (PC 200 ). 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 PC 200 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 PC 200 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.