Effects of long-term application of metoprolol and propranolol in a rat model of smoking.

ABSTRACT

Beta-blockers, especially selective ß1 -adrenoceptor antagonists, are often used to treat cardiovascular disease, even when complicated by chronic obstructive pulmonary disease. The association of beta-blocker selectivity and treatment effects is disputed, and the curative effects and side-effects of various antagonists may differ. Herein we investigated the effects of 1 months treatment with the selective ß1 -adrenoceptor antagonist metoprolol and the non-selective ß-adrenoceptor antagonist propranolol on pulmonary function and pathology in a 4-month rat model of passive cigarette smoke exposure and explored potential mechanisms of action. Lung function and general pathological changes were evaluated after 4 months exposure to cigarette smoke, with metoprolol and propranolol treatment (50 and 25 mg/kg per day, respectively; intragastrically) during the last month. Cytokine and mucin levels in bronchoalveolar lavage fluid (BALF) were determined by ELISA, whereas ß1 - and ß2 -adrenoceptor expression in the lungs was evaluated by immunohistochemistry and western blot analysis. Chronic treatment with metoprolol and propranolol did not exacerbate peak expiratory flow or intra-airway pressure in rats exposed to cigarette smoke. Propranolol significantly attenuated inflammatory cell infiltration, cytokine levels (tumour necrosis factor-α and interleukin-8) in BALF or mucus secretion, whereas metoprolol reduced only smooth muscle proliferation. Moreover, propranolol treatment was associated (albeit not significantly) with restoring ß2 -adrenoceptor expression in airway epithelia. Propranolol had a more beneficial effect on cigarette smoking-induced lung damage than metoprolol in a smoking rat model that may be associated with restoration of endogenous ß2 -adrenoceptor density in the airway epithelial cells.