ROLE OF ADRENERGIC NERVOUS-SYSTEM IN CIGARETTE SMOKE-INDUCED BRONCHOCONSTRICTION IN GUINEA-PIGS

The goal of this study was to clarify the role of the adrenergic nervo us system in bronchoconstriction induced by exposure to cigarette smok e in guinea pigs. Artificially ventilated animals were exposed to 160 puffs of smoke for 8 min. Bronchoconstriction was assessed as a percen tage of the baseline total pulmonary resistance (R-L). The effects of pretreatment with phentolamine (0.1 mg/kg, i.v.), propranolol (1 mg/kg , i.v.), and/or atropine (1 mg/kg, i.v.) were evaluated. Exposure to c igarette smoke caused significant bronchoconstriction. Phentolamine, a n alpha-adrenoceptor antagonist, significantly inhibited cigarette smo ke-induced bronchoconstriction, while propranolol, a beta-adrenoceptor antagonist, significantly enhanced it. Combined use of these compound s further enhanced the bronchoconstriction. All of modulations of the bronchoconstriction by adrenoceptor antagonists were completely abolis hed by pretreatment with atropine. Phentolamine and/or propranolol had no effect on the bronchoconstriction induced by inhaled acetylcholine . Pretreatment with yohimbine (0.5 mg/kg, i.v.), a selective alpha(2)- adrenoceptor antagonist, showed modulatory effects similar to those of phentolamine on cigarette smoke-induced bronchoconstriction. These re sults suggest that cigarette smoke-induced bronchoconstriction is regu lated by the prejunctional modulation of the cholinergic system via al pha- and beta-adrenoceptors. This mechanism may be modulated by the au toregulation of adrenergic nerves via the alpha(2)-autoreceptor. (C) 1 998 Elsevier Science B.V. All rights reserved.