Angiotensin (1–7) facilitates cardioprotection of ischemic preconditioning on ischemia–reperfusion-challenged rat heart

Ischemic preconditioning (IPC) is one of the most promising strategies used to protect the myocardium from ischemia–reperfusion injury. Ang (1–7) exhibits cardioprotective activity; however, its therapeutic potential on IPC-induced cardioprotection has not been reported in ischemia–reperfusion injury till date. Therefore, the first set of experiment was designed to evaluate the direct effect of Ang (1–7), in perfusion medium, on cardioprotective activity of IPC in rat heart challenged to ischemia–reperfusion injury. In addition, the acute and chronic effects of pretreated Ang (1–7) were investigated on cardioprotection of IPC in ischemia–reperfusion-challenged hearts in subsequent sets of experiments. The results showed that Ang (1–7) potentiated the IPC-induced increase in coronary flow and heart rate, decrease in lactate dehydrogenase and creatine kinase activity, ventricular fibrillation, and infarct size in ischemia–reperfusion-challenged animals in direct and chronic sets of experiments. Further, Ang (1–7) enhanced the IPC-induced attenuation in mitochondrial dysfunction, oxidative stress, and apoptosis in ischemia–reperfusion-challenged hearts in both sets of experiments. A-779, Mas receptor antagonist, abrogated potentiation effects of Ang (1–7) on IPC-induced cardioprotection in ischemia–reperfusion-challenged rats in the above set of experiments. These observations indicate that Ang (1–7)/Mas receptor activation could be a potential adjuvant to IPC during ischemia–reperfusion-induced cardiac injury.