Metoprolol-Mediated Amelioration of Sympathetic Nerve Sprouting after Myocardial Infarction

OBJECTIVES: Systemic or local inflammation causes cardiac nerve sprouting and consequent arrhythmia. Metoprolol can prevent sympathetic nerve remodeling after myocardial infarction (MI), but the underlying mechanism is unclear. In this study, we evaluated the role of metoprolol in ameliorating sympathetic sprouting. METHODS: Rabbits underwent ligation of the coronary artery for MI. MI rabbits received metoprolol or saline for 7 days. Immunohistochemistry was used to measure cardiac nerve sprouting and sympathetic innervations. Nuclear factor-κB (NF-κB) DNA binding activity was analyzed by electrophoretic mobility shift assay. The protein levels of NF-κB p65, inhibitor κBα (IκBα) and nerve growth factor (NGF) were detected by Western blot analysis. The mRNA levels of NGF, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were examined by quantitative real-time PCR. RESULTS: MI rabbits showed nerve sprouting and sympathetic hyperinnervation. In MI rabbits, as compared with saline treatment, metoprolol reduced NF-κB DNA binding activity and NF-κB p65 level, and increased IκBα level. Moreover, metoprolol downregulated IL-1β, TNF-α and NGF levels, and reduced the density of sympathetic nerve fibers. CONCLUSIONS: Metoprolol ameliorates sympathetic nerve sprouting in rabbits after MI and is associated in part with inhibiting NF-κB activity.