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 nervous system in bronchoconstriction induced by exposure to cigarette smoke in guinea pigs. Artificially ventilated animals were exposed to 160 puffs of smoke for 8 min. Bronchoconstriction was assessed as a percentage of the baseline total pulmonary resistance (RL). 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 cigarette smoke caused significant bronchoconstriction. Phentolamine, an alpha-adrenoceptor antagonist, significantly inhibited cigarette smoke-induced bronchoconstriction, while propranolol, a beta-adrenoceptor antagonist, significantly enhanced it. Combined use of these compounds further enhanced the bronchoconstriction. All of modulations of the bronchoconstriction by adrenoceptor antagonists were completely abolished 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 alpha2-adrenoceptor antagonist, showed modulatory effects similar to those of phentolamine on cigarette smoke-induced bronchoconstriction. These results suggest that cigarette smoke-induced bronchoconstriction is regulated by the prejunctional modulation of the cholinergic system via alpha- and beta-adrenoceptors. This mechanism may be modulated by the autoregulation of adrenergic nerves via the alpha2-autoreceptor.