Abstract
Aim: Ischemia and reperfusion (IR) injury is a serious problem that is occured during thrombolytic therapy, organ transplantation, coronary angioplasty, and cardiopulmonary bypass. There is an increase in the number of AT2 receptors in some pathological conditions such as cardiac hypertrophy, myocardial infarction, congestive heart failure. This study was designed to investigate the effects AT2 receptor agonist Novokinin on infarct size, caveolin-1 (CAV-1), HSP90, ADMA, NADPH oxidase and Rhokinase associated to endothelial dysfunction and oxidative stress, and NFκB and TLR-4 levels induced by inflammation on myocardial IR. Methods: The experimental groups: Sham (C), Novokinin (N), IR and IRN. Novokinin was performed with infusion pump before ischemia, and during IR. The left main coronary artery was occluded for 30 minutes ischemia followed by 120 minutes reperfusion in anesthetized rats. CAV-1, HSP90, and NFκB levels were measured by the quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), ADMA, TLR-4, NADPH oxidase, and Rhokinase levels were measured by ELISA, infarct size was measured by ImageJ, an image analysis software, in the heart tissue. Results: NFκB, HSP90, NADPH oxidase and TLR-4 levels increased with IR and significantly decreased with Novokinin. CAV-1 levels were not different between the groups. ADMA and Rhokinase levels were increased due to IR but decreased with Novokinin. Novokinin reduced infarct size due to IR. Conclusion: Our results showed that, ADMA, HSP90, NFκB, 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.
Highlights
Ischemic heart disease remains one of the most important causes of morbidity and mortality throughout the world [1]
This study was designed to investigate the effects AT2 receptor agonist Novokinin on infarct size, caveolin-1 (CAV-1), heat shock protein 90 (HSP90), Asymmetrical dimethyl arginine (ADMA), NADPH oxidase and Rhokinase associated to endothelial dysfunction and oxidative stress, and NFκB and Toll-like receptor 4 (TLR-4) levels induced by inflammation on myocardial Ischemia and reperfusion (IR)
CAV-1, HSP90, and NFκB levels were measured by the quantitative reverse transcriptase polymerase chain reaction, ADMA, TLR-4, NADPH oxidase, and Rhokinase levels were measured by ELISA, infarct size was measured by ImageJ, an image analysis software, in the heart tissue
Summary
Ischemic heart disease remains one of the most important causes of morbidity and mortality throughout the world [1]. The most common form is “coronary atherosclerotic heart disease” and the coronary blood flow to myocardium due to atherosclerotic plaques and vasospasm is reduced [2]. Ischemia and reperfusion (IR) injury is a serious problem that is occurred during a variety of medical and surgical procedures, such as thrombolytic therapy, organ transplantation, coronary angioplasty, and cardiopulmonary bypass [3]. Endothelial dysfunction, oxidative stress and inflammation are among the most common mechanisms of IR injury [4]. Nuclear factor kappa-B (NFκB) is responsible for the production of inflammatory genes redox-sensitive transcription factors, which activate in response to oxidative stress. NFκB activation stimulates the expression of proinflammatory cytokines. NFκB pathway is involved in the pathological process and activates cell death pathways [5]
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