title: Thromboxane causes airway hyperresponsiveness after cigarette smoke-induced neurogenic inflammation.
abstract: We investigated the role of neurogenic inflammation and the subsequent mechanisms in cigarette smoke-induced airway hyperresponsiveness in guinea pigs. Exposure to cigarette smoke was carried out at tidal volume for 3 min. Airway responsiveness to histamine was determined before and after smoke exposure followed by bronchoalveolar lavage (BAL). Plasma extravasation was evaluated by measuring the extravasation of Evans blue dye in the airway. Cigarette smoke produced significant airway hyperresponsiveness and plasma extravasation, with an influx of neutrophils in BAL fluid. FK-224 (10 mg/kg i.v.), a tachykinin antagonist at NK1 and NK2 receptors, significantly inhibited these changes. The thromboxane (Tx) B2 concentration was increased in BAL fluid after smoke exposure and was significantly inhibited by FK-224. OKY-046 (10 mg/kg i.v.), a Tx synthase inhibitor, significantly inhibited airway hyperresponsiveness but had no effect on neutrophil influx or plasma extravasation. The results suggest that neurogenic inflammation and the subsequent generation of Tx in the airway are important in the development of the airway hyperresponsiveness induced by cigarette smoke.
authors.affiliation: Research Institute for Diseases of the Chest, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Matsumoto
authors.forename: H
authors.initials: H
authors.lastname: Aizawa
authors.forename: H
authors.initials: H
authors.lastname: Inoue
authors.forename: M
authors.initials: M
authors.lastname: Shigyo
authors.forename: S
authors.initials: S
authors.lastname: Takata
authors.forename: N
authors.initials: N
authors.lastname: Hara
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D007249:Inflammation / Q000139:chemically induced; D008297:Male; D012137:Respiratory System / Q000187:drug effects*; D012907:Smoking / Q000503:physiopathology*; D013931:Thromboxanes / Q000494:pharmacology*
chemical_list: D013931:Thromboxanes