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

Abstract

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.