Nebivolol protects against myocardial infarction injury via stimulation of beta 3-adrenergic receptors and nitric oxide signaling.
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.
Department of Cardiology, The Second Artillery General Hospital of Chinese People's Liberation Army, Beijing, China.
Zheng
Z
Zhang
Department of Cardiology, The Second Artillery General Hospital of Chinese People's Liberation Army, Beijing, China.
Liping
L
Ding
Department of Cardiology, The Second Artillery General Hospital of Chinese People's Liberation Army, Beijing, China.
Zhitao
Z
Jin
Department of Cardiology, The Second Artillery General Hospital of Chinese People's Liberation Army, Beijing, China.
Guojie
G
Gao
Department of Cardiology, The Second Artillery General Hospital of Chinese People's Liberation Army, Beijing, China.
Huijun
H
Li
Department of Cardiology, The Second Artillery General Hospital of Chinese People's Liberation Army, Beijing, China.
Lijuan
L
Zhang
Department of Cardiology, The Second Artillery General Hospital of Chinese People's Liberation Army, Beijing, China.
Lina
L
Zhang
Department of Cardiology, The Second Artillery General Hospital of Chinese People's Liberation Army, Beijing, China.
Xin
X
Lu
Department of Cardiology, The Second Artillery General Hospital of Chinese People's Liberation Army, Beijing, China.
Lihua
L
Hu
Department of Cardiology, The Second Artillery General Hospital of Chinese People's Liberation Army, Beijing, China.
Bingwei
B
Lu
Department of Cardiology, The Second Artillery General Hospital of Chinese People's Liberation Army, Beijing, China.
Xiongjun
X
Yu
Department of Cardiology, The Second Artillery General Hospital of Chinese People's Liberation Army, Beijing, China.
Taohong
T
Hu
D058671:Adrenergic beta-1 Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis; D001158:Arteries / Q000378:metabolism; D001578:Benzopyrans / Q000494:pharmacology*; D001794:Blood Pressure; D004452:Echocardiography; D004983:Ethanolamines / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000517:prevention & control*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D000068577:Nebivolol; D009569:Nitric Oxide / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism*; D015398:Signal Transduction
C097869:3-(2-ethylphenoxy)-1-(1,2,3,4-tetrahydronaphth-1-ylamino)-2-propanol oxalate; D058671:Adrenergic beta-1 Receptor Antagonists; D001578:Benzopyrans; D004983:Ethanolamines; D011412:Propanolamines; D022702:Receptors, Adrenergic, beta-3; D000068577:Nebivolol; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; C496321:Nos1 protein, mouse; C496315:Nos3 protein, mouse; D019331:NG-Nitroarginine Methyl Ester