Cigarette smoke-induced bronchoconstriction: causative agents and role of thromboxane receptors

Ju-Lun Hong and Lu-Yuan Lee Department of Physiology, University of Kentucky, Lexington, Kentucky 40536-0084 Received 14 December 1995; accepted in final form 12 July 1996. Hong, Ju-Lun, and Lu-Yuan Lee. Cigarette smoke-induced bronchoconstriction: causative agents and role of thromboxane receptors. J. Appl. Physiol. 81(5): 2053-2059, 1996. Inhalation of cigarette smoke induces a biphasic bronchoconstriction in guinea pigs: the first phase is induced by a combination of cholinergic reflex and tachykinins, whereas the second phase involves cyclooxygenase metabolites (J.-L. Hong, I. W. Rodger, and L.-Y. Lee. J. Appl. Physiol. 78: 2260-2266, 1995). This study was carried out to further determine the causative agents in the smoke and the types of prostanoid receptors and endogenous prostanoids mediating the bronchoconstriction. Inhalation of 10 ml of high-nicotine cigarette smoke consistently elicited the biphasic bronchoconstriction in anesthetized and artificially ventilated guinea pigs. Pretreatment with hexamethonium (10 mg/kg iv) significantly reduced the first-phase bronchoconstriction but did not have any measurable effect on the second-phase response. In sharp contrast, gas-phase smoke did not elicit any bronchoconstrictive effect. Furthermore, when the animals were challenged with low-nicotine cigarette smoke, only a single second-phase response was evoked, accompanied by increases in thromboxane (Tx) B 2 (a stable metabolite of TxA 2 ), prostaglandin (PG) D 2 , PGF 2 in the bronchoalveolar lavage fluid. The bronchoconstrictive response induced by low-nicotine smoke was completely prevented by pretreatment with SQ-29548 (0.3 mg/kg iv), a TxA 2 -receptor antagonist. These results indicate that 1 ) nicotine is the primary causative agent responsible for the first-phase bronchoconstriction and 2 ) nonnicotine smoke particulates evoke the release of TxA 2 , PGD 2 , and PGF 2 , which act on TxA 2 receptors on airway smooth muscles and induce the second-phase response to cigarette smoke. hexamethonium; SQ-29548; tachykinins; guinea pigs; prostaglandins 0161-7567/96 $5.00 Copyright © 1996 the American Physiological Society