The effects of a specific tachykinin receptor antagonist FK-224 on ozone-induced airway hyperresponsiveness and inflammation.

Abstract

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 (RL) 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 RL 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.

• Authors: H Aizawa, H Koto, H Nakano, H Inoue, K Matsumoto, S Takata, M Shigyo, N Hara
• Journal: Respirology (Carlton, Vic.) (Respirology) Vol. 2 Issue 4 Pg. 261-5 (Dec 1997) ISSN: 1323-7799 [Print] Australia
• PMID: 9525295 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Peptides, Cyclic
• Receptors, Tachykinin
• FK 224
• Ozone

Topics

• Airway Resistance (drug effects, physiology)
• Animals
• Bronchial Hyperreactivity (chemically induced, drug therapy)
• Bronchoalveolar Lavage Fluid (cytology)
• Disease Models, Animal
• Guinea Pigs
• Inflammation (drug therapy)
• Infusions, Intravenous
• Male
• Ozone
• Peptides, Cyclic (administration & dosage)
• Receptors, Tachykinin (antagonists & inhibitors)
• Reference Values