Effects of long-term application of metoprolol and propranolol in a rat model of smoking.
Clin Exp Pharmacol Physiol
; 41(9): 708-15, 2014 Sep.
Article
em En
| MEDLINE
| ID: mdl-24837395
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.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Propranolol
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Poluição por Fumaça de Tabaco
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Fumar
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Lesão Pulmonar
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Metoprolol
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article