The effects of at2 receptor agonist novokinin on oxidative stress, inflammation and necrosis area due to myocardial ischemia-reperfusion

Ischemia and reperfusion (IR) injury is a serious problem that is occured during a variety of medical and surgical procedures, such as thrombolytic therapy, organ transplantation, coronary angioplasty, and cardiopulmonary bypass and the renin-angiotensin system plays an important role in this damage. In contrast to the AT1 receptors, AT2 receptors have vasodilator, anti-proliferative, proapoptotic effects. In pathological conditions such as cardiac hypertrophy, myocardial infarction, congestive heart failure there is an increase in the number of AT2 receptors. This study was designed to investigate the effects of AT2 receptor agonist Novokinin on necrosis area, CAV-1, HSP90, ADMA, NADPH oxidase and Rhokinase associated due to endothelial dysfunction and oxidative stress, and increased NF?B and Toll-like 4 receptor (TLR-4) levels induced by inflammation on myocardial IR. The experimental animals were divided into four groups in this study: Control, Novokinin, IR and IR+Novokinin (IRN). Drug administrations was performed with infusion pump via cannula were placed the jugular vein under general anesthesia before ischemia, and during IR. The left main coronary artery was occluded for 30 minutes ischemia followed by 120 minutes reperfusion in rats. At the end of the experimental period, CAV-1, HSP90, and NFKB levels were measured by RT-PCR, ADMA, TLR-4, NADPH oxidase, and Rhokinase levels were measured by ELISA, necrosis area was measured by ImageJ, an image analysis software, in the heart tissue. Mean blood pressure significantly decreased at the begining of ischemia and reperfusion and at the end of ischemia in IRN group compared to IR group. NFKB, HSP90, NADPH oxidase and TLR-4 levels increased with IR and significantly decreased with the application of novokinin. CAV-1 levels did not differ between the groups. The increases in the levels of ADMA and Rhokinase due to IR have been prevented by the application of novokinin. Novokinin reduced necrosis area due to IR. Our results reveals that, ADMA, HSP90, NFKB, TLR-4, Rhokinase, and NADPH oxidase levels play important roles on IR injury. AT2 receptor agonist Novokinin may affect positively oxidative changes, inflammation, and endothelial function in myocardial IR injury. Keywords: Ischemia-reperfusion, AT2 receptor, ADMA, NF?B, HSP90