title: β3-Adrenoreceptor stimulation protects against myocardial infarction injury via eNOS and nNOS activation.
abstract: β3-adrenergic receptor (AR) and the downstream signaling, nitric oxide synthase (NOS) isoforms, have been emerged as novel modulators of heart function and even potential therapeutic targets for cardiovascular diseases. However, it is not known whether β3-AR plays cardioprotective effects against myocardial infarction (MI) injury. Therefore, the present study was designed to determine the effects of β3-AR on MI injury and to elucidate the underlying mechanism. MI model was constructed by left anterior descending (LAD) artery ligation. Animals were administrated with β3-AR agonist BRL37344 (BRL) or β3-AR inhibitor SR59230A (SR) respectively at 0.1 mg/kg/hour one day after MI operation. The scar area, cardiac function and the apoptosis of myocardial were assessed by Masson's trichrome stain, echocardiography and TUNEL assay respectively. Western blot analysis was performed to elucidate the expressions of target proteins. β3-AR activation with BRL administration significantly attenuated fibrosis and decreased scar area after MI. Moreover, BRL also preserved heart function, and reduced the apoptosis of cardiomyocyte induced by MI. Furthermore, BRL treatment altered the phosphorylation status of endothelial NOS (eNOS) and increased the expression of neuronal NOS (nNOS). These results suggested that β3-AR stimulation has a substantial effect on recovery of heart function. In addition, the activations of both eNOS and nNOS may be associated with the cardiac protective effects of β3-AR.
authors.affiliation: Department of Cardiology, Tangdu Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Niu
authors.affiliation: Department of Cardiology, Tangdu Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Lianyou
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, Tangdu Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Cardiology, Tangdu Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Yusheng
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Department of Cardiology, Tangdu Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Cadet Brigade of Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Zongqiang
authors.initials: Z
authors.lastname: Lv
authors.affiliation: Department of Cardiology, Tangdu Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Jianghong
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Sun
authors.affiliation: Department of Cardiology, Tangdu Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Qiangsun
authors.initials: Q
authors.lastname: Zheng
mesh_terms: D058667:Adrenergic beta-3 Receptor Agonists / Q000494:pharmacology; D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects; D004983:Ethanolamines / Q000494:pharmacology; D005355:Fibrosis; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism*; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D058667:Adrenergic beta-3 Receptor Agonists; D004983:Ethanolamines; D022702:Receptors, Adrenergic, beta-3; C057368:BRL 37344; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III