CIGARETTE SMOKE-INDUCED BRONCHOCONSTRICTION - CAUSATIVE AGENTS AND ROLE OF THROMBOXANE RECEPTORS

Inhalation of cigarette smoke induces a biphasic bronchoconstriction i n guinea pigs: the first phase is induced by a combination of choliner gic reflex and tachykinins, whereas the second phase involves cyclooxy genase 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 d etermine the causative agents in the smoke and the types of prostanoid receptors and endogenous prostanoids mediating the bronchoconstrictio n. Inhalation of 10 mi of high-nicotine cigarette smoke consistently e licited the biphasic bronchoconstriction in anesthetized and artificia lly 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 effec t. Furthermore, when the animals were challenged with low-nicotine cig arette smoke, only a single second-phase response was evoked, accompan ied by increases in thromboxane (Tx) B-2 (a stable metabolite of TxA(2 )), prostaglandin (PG) D-2, PGF(2 alpha) 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) nicotin e is the primary causative agent responsible for the first-phase bronc hoconstriction and 2) nonnicotine smoke particulates evoke the release of TxA(2), PGD(2), and PGF(2 alpha), which act on TxA(2) receptors on airway smooth muscles and induce the second-phase response to cigaret te smoke.