Nebivolol protects against myocardial infarction injury via stimulation of beta 3-adrenergic receptors and nitric oxide signaling.

Abstract

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.

• Authors: Zheng Zhang, Liping Ding, Zhitao Jin, Guojie Gao, Huijun Li, Lijuan Zhang, Lina Zhang, Xin Lu, Lihua Hu, Bingwei Lu, Xiongjun Yu, Taohong Hu
• Journal: PloS one (PLoS One) Vol. 9 Issue 5 Pg. e98179 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 24849208 (Publication Type: Journal Article)

Chemical References

• 3-(2-ethylphenoxy)-1-(1,2,3,4-tetrahydronaphth-1-ylamino)-2-propanol oxalate
• Adrenergic beta-1 Receptor Antagonists
• Benzopyrans
• Ethanolamines
• Propanolamines
• Receptors, Adrenergic, beta-3
• Nebivolol
• Nitric Oxide
• Nitric Oxide Synthase Type I
• Nitric Oxide Synthase Type III
• Nos1 protein, mouse
• Nos3 protein, mouse
• NG-Nitroarginine Methyl Ester

Topics

• Adrenergic beta-1 Receptor Antagonists (pharmacology)
• Animals
• Apoptosis
• Arteries (metabolism)
• Benzopyrans (pharmacology)
• Blood Pressure
• Echocardiography
• Ethanolamines (pharmacology)
• Heart (drug effects)
• Hemodynamics
• Male
• Mice
• Mice, Inbred C57BL
• Myocardial Infarction (prevention & control)
• NG-Nitroarginine Methyl Ester (pharmacology)
• Nebivolol
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase Type I (metabolism)
• Nitric Oxide Synthase Type III (metabolism)
• Propanolamines (pharmacology)
• Receptors, Adrenergic, beta-3 (metabolism)
• Signal Transduction