Journal of Applied Physiology AJP: Gastrointestinal and Liver Physiology
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J Appl Physiol 81: 2358-2364, 1996;
8750-7587/96 $5.00
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Journal of Applied Physiology
Vol. 81, No. 6, pp. 2358-2364, December 1996
GAS EXCHANGE, MECHANICS, AND AIRWAYS

Thromboxane causes airway hyperresponsiveness after cigarette smoke-induced neurogenic inflammation

Koichiro Matsumoto, Hisamichi Aizawa, Hiromasa Inoue, Mutsumi Shigyo, Shohei Takata, and Nobuyuki Hara

Research Institute for Diseases of the Chest, Faculty of Medicine, Kyushu University, Higashiku, Fukuoka 812, Japan

Received 1 February 1996; accepted in final form 22 July 1996.

Matsumoto, Koichiro, Hisamichi Aizawa, Hiromasa Inoue, Mutsumi Shigyo, Shohei Takata, and Nobuyuki Hara. Thromboxane causes airway hyperresponsiveness after cigarette smoke-induced neurogenic inflammation. J. Appl. Physiol. 81(6): 2358-2364, 1996.---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 iv), 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 iv), 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.

guinea pigs; plasma extravasation; neutrophils

0161-7567/96 $5.00 Copyright © 1996 the American Physiological Society




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