Angiotensin 1–7 Attenuates the Development of Ischemia–Reperfusion‐Induced Arrhythmia in Rats: Electrophysiology, Molecular, and Immunohistochemical Study

Arrhythmia is a common and serious global health problem, contributing to cardiovascular morbidity and mortality. The cardiac muscle is susceptible to ischemia-reperfusion (I/R) injury, which can lead to fatal arrhythmias during open-heart surgery. We investigated the potential prophylactic effect of angiotensin 1-7 (Ang 1-7) using an in vivo rat model of I/R injury and examined the underlying mechanisms. Rats were treated with Ang 1-7 (1 mg/kg, IP) 30 min before the surgical procedures. Twenty-four rats were equally divided into four groups: sham control, sham-treated with Ang 1-7, I/R injury group, and I/R injury group treated with Ang 1-7. In vivo I/R injury was induced by clamping the left coronary artery for 30 min, followed by 1 hour of reperfusion. The I/R group showed abnormal electrophysiological changes and arrhythmic episodes during electrocardiography (ECG) recording, increased oxidative stress, downregulation of peroxisome proliferator-activated receptor gamma (PPAR-γ), and upregulation of C-X-C motif chemokine ligand 16 (CXCL16) expression in cardiac tissue, which increased cardiac NF-kB expression and IL-17 levels. Moreover, I/R injury caused significant histological disruption and increased cyclooxygenase 2 (COX-2) and heat shock protein 90 (HSP90) immunoreactions, correlating with the extent of cardiac damage. However, preoperative Ang 1-7 administration significantly improved the electrophysiological, biochemical, and histopathological changes induced by I/R injury. This study demonstrated that Ang 1-7 exerted protective anti-arrhythmic, anti-inflammatory, and pro-healing effects by upregulating PPAR-γ and downregulating CXCL16, IL-17, and NF-kB pathways, suggesting it is a promising cardioprotective agent for preventing arrhythmias induced by I/R injury.