sr-59230a and Myocardial-Infarction

Myocardial infarction (MI) and osteoporotic fracture are leading causes of morbidity and mortality, and epidemiological evidence linking their incidence suggests possible crosstalk. MI can exacerbate atherosclerosis through the sympathetic nervous system (SNS) activation and β

Topics: Absorptiometry, Photon; Animals; Body Composition; Bone Density; Bone Diseases, Metabolic; Femur; Hematopoietic Stem Cells; Lumbar Vertebrae; Male; Mice; Mice, Inbred C57BL; Monocytes; Myocardial Infarction; Osteoclasts; Osteoporotic Fractures; Propanolamines; Receptors, Adrenergic, beta-3; Stress, Mechanical; Sympathetic Nervous System; X-Ray Microtomography

Nebivolol, third-generation β-blocker, may activate β3-adrenergic receptor (AR), which has been emerged as a novel and potential therapeutic targets for cardiovascular diseases. However, it is not known whether nebivolol administration plays a cardioprotective effect against myocardial infarction (MI) injury. Therefore, the present study was designed to clarify the effects of nebivolol on MI injury and to elucidate the underlying mechanism. MI model was constructed by left anterior descending (LAD) artery ligation. Nebivolol, β3-AR antagonist (SR59230A), Nitro-L-arginine methylester (L-NAME) or vehicle was administered for 4 weeks after MI operation. Cardiac function was monitored by echocardiography. Moreover, the fibrosis and the apoptosis of myocardium were assessed by Masson's trichrome stain and TUNEL assay respectively 4 weeks after MI. Nebivolol administration reduced scar area by 68% compared with MI group (p<0.05). Meanwhile, nebivolol also decreased the myocardial apoptosis and improved the heart function after MI (p<0.05 vs. MI). These effects were associated with increased β3-AR expression. Moreover, nebivolol treatment significantly increased the phosphorylation of endothelial NOS (eNOS) and the expression of neuronal NOS (nNOS). Conversely, the cardiac protective effects of nebivolol were abolished by SR and L-NAME. These results indicate that nebivolol protects against MI injury. Furthermore, the cardioprotective effects of nebivolol may be mediated by β3-AR-eNOS/nNOS pathway.

Topics: Adrenergic beta-1 Receptor Antagonists; Animals; Apoptosis; Arteries; Benzopyrans; Blood Pressure; Echocardiography; Ethanolamines; Heart; Hemodynamics; Male; Mice; Mice, Inbred C57BL; Myocardial Infarction; Nebivolol; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase Type I; Nitric Oxide Synthase Type III; Propanolamines; Receptors, Adrenergic, beta-3; Signal Transduction