Effects of long-term application of metoprolol and propranolol in a rat model of smoking.
Beta-blockers, especially selective β1 -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 β1 -adrenoceptor antagonist metoprolol and the non-selective β-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 β1 - and β2 -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 β2 -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 β2 -adrenoceptor density in the airway epithelial cells.
Department of Respiratory Medicine and Institute of Vascular Medicine, Peking University Third Hospital, Beijing, China; Beijing Key Laboratory of Cardiovascular Receptors Research, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health, Beijing, China.
Yujiao
Y
Zhou
Ming
M
Xu
Yuan
Y
Zhang
Yang
Y
Guo
Youyi
Y
Zhang
Bei
B
He
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D016209:Interleukin-8 / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D055370:Lung Injury / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D023421:Models, Animal; D009093:Mucus / Q000378:metabolism; D011433:Propranolol / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects*; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000319:Adrenergic beta-Antagonists; D016209:Interleukin-8; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D014028:Tobacco Smoke Pollution; D014409:Tumor Necrosis Factor-alpha; D011433:Propranolol; D008790:Metoprolol
airway inflammation; beta-blocker; lung function; mucin; smoking rat model; β-adrenoceptor