首页> 外文期刊>American Journal of Physiology >Stimulation of A2A-adenosine receptors after myocardial infarction suppresses inflammatory activation and attenuates contractile dysfunction in the remote left ventricle.
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Stimulation of A2A-adenosine receptors after myocardial infarction suppresses inflammatory activation and attenuates contractile dysfunction in the remote left ventricle.

机译:心肌梗死后刺激A2A-腺苷受体抑制炎症激活并减轻远端左心室的收缩功能障碍。

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摘要

Following myocardial infarction (MI), contractile dysfunction develops not only in the infarct zone but also in noninfarcted regions of the left ventricle remote from the infarct zone. Inflammatory activation secondary to MI stimulates inducible nitric oxide synthase (iNOS) induction with excess production of nitric oxide. We hypothesized that the anti-inflammatory effects of selective A(2A)-adenosine receptor (A(2A)AR) stimulation would suppress inflammation and preserve cardiac function in the remote zone early after MI. A total of 53 mice underwent 60 min of coronary occlusion followed by 24 h of reperfusion. The A(2A)AR agonist (ATL146e, 2.4 microg/kg) was administered intraperitoneally 1, 3, and 6 h postreperfusion. Because of the 1-h delay in treatment after MI, ATL146e had no effect on infarct size, as demonstrated by contrast-enhanced cardiac MRI (n = 18) performed 24 h post-MI. ATL146e did however preserve global cardiac function at that time by limiting contractile dysfunction in remote regions [left ventricle wall thickening: 51 +/- 4% in treated (n 9) vs. 29 +/- 3% in nontreated groups (n immunohistochemistry, and Western blot analysis indicated that iNOS mRNA and protein expression were significantly reduced by ATL146e treatment in both infarcted and noninfarcted zones. Similarly, elevations in plasma nitrate-nitrite after MI were substantially blunted by ATL146e (P < 0.01). Finally, treatment with ATL146e reduced NF-kappaB activation in the myocardium by over 50%, not only in the infarct zone but also in noninfarcted regions (P < 0.05). In conclusion, A(2A)AR stimulation after MI suppresses inflammatory activation and preserves cardiac function, suggesting the potential utility of A(2A)AR agonists against acute heart failure in the immediate post-MI period.
机译:心肌梗塞(MI)后,收缩功能障碍不仅在梗塞区发展,而且在远离梗塞区的左心室非梗塞区发展。继发于MI的炎症激活刺激诱导型一氧化氮合酶(iNOS)的诱导,并产生过量的一氧化氮。我们假设选择性的A(2A)-腺苷受体(A(2A)AR)刺激的抗炎作用将抑制炎症并在MI后早期在偏远地区保留心脏功能。总共53只小鼠进行了60分钟的冠状动脉闭塞,然后再灌注24小时。在再灌注后1、3和6小时腹膜内给予A(2A)AR激动剂(ATL146e,2.4微克/千克)。由于心肌梗死后1小时的治疗延迟,ATL146e对梗死面积没有影响,如心梗后24小时进行的对比增强心脏MRI(n = 18)所证明的。但是,ATL146e当时确实通过限制偏远地区的收缩功能障碍来维持整体心脏功能[左心室壁增厚:治疗组(n 9)为51 +/- 4%,未治疗组为29 +/- 3%(n免疫组化, Western blot分析表明,在梗死区和非梗死区中,ATL146e处理均显着降低了iNOS的mRNA和蛋白表达; ATL146e使MI后血浆硝酸盐-亚硝酸盐的升高明显减弱(P <0.01)。不仅在梗死区域而且在非梗死区域将心肌中的NF-κB激活降低了50%以上(P <0.05)。总之,MI后的A(2A)AR刺激抑制了炎症激活并保持了心脏功能,提示MI后立即使用A(2A)AR激动剂对急性心力衰竭的潜在效用。

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