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This study investigated the protective effects of the \u03b22\u2010adrenergic receptor (\u03b22\u2010AR) agonist clenbuterol against ischemia\/reperfusion\u2010induced arrhythmias and the underlying mechanism. Anesthetized rats were subjected to 10\u2010min left coronary artery occlusion and 10\u2010min reperfusion in\u00a0vivo. Langendorff\u2010perfused mice hearts were exposed to 10\u2010min global ischemia and 10\u2010min reperfusion. Arrhythmic events were recorded during early reperfusion. Hearts were collected for measuring nitric oxide (NO) concentration and immunoblotting of Connexin 43 (Cx43), endothelial nitric oxide synthase (eNOS), and protein kinase B (Akt). After the ischemia\/reperfusion injury in anesthesia rats, clenbuterol markedly reduced the duration and incidence of ventricular tachycardia and ventricular fibrillation, and arrhythmia score, which was abrogated by selective \u03b22\u2010AR antagonist or Cx43 inhibitor. Furthermore, a marked increase in dephosphorylated Cx43 expression and a decrease in the ratio of phosphorylated Cx43 to total Cx43 were observed after the ischemia\/reperfusion injury. Mechanistically, clenbuterol increased the phosphorylation of e\u2010NOS and NO concentration, while L\u2010NAME abolished Cx43 phosphorylation and the protective effect of clenbuterol. Clenbuterol also promoted Akt phosphorylation, and blockade of Akt inhibited eNOS phosphorylation and NO production, as well as Cx43 phosphorylation and protective effect of clenbuterol. The present study elucidates that \u03b22\u2010AR stimulation activates the Akt\/eNOS signaling pathway, augments NO bioavailability, maintains Cx43 phosphorylation, and prevents Cx43 remodeling, ultimately attenuating arrhythmia induced by ischemia\/reperfusion.<\/jats:p>","DOI":"10.1002\/prp2.70070","type":"journal-article","created":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T15:45:26Z","timestamp":1738079126000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["\u03b22\u2010Adrenergic Receptor Agonist Clenbuterol Protects Against Acute Ischemia\/Reperfusion\u2010Induced Arrhythmia by Regulation of Akt\/<scp>eNOS<\/scp>\/<scp>NO<\/scp>\/Cx43 Signaling Pathway"],"prefix":"10.1002","volume":"13","author":[{"given":"Jing","family":"Fu","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Basic Medicine Tongji Medical College, Huazhong University of Science and Technology  Wuhan 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