Effect of losartan on NOX2 transcription following acute myocardial ischemia-reperfusion

Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-2 (Nox2) is one of the predominant sources of ROS production during myocardial ischemia-reperfusion and can be induced by angiotensin II. The evidence suggests that pharmacological blockers of renin-angiotensin system can exert direct tissue effects independent of their ability to regulate blood pressure. The mechanism(s) responsible for such direct effects are not well understood. The aim of this study was to investigate the early changes of cardiac NOX2 gene transcription after myocardial ischemiareperfusion in rats treated with losartan, an angiotensin type 1 (AT1) receptor blocker. Wistar rats were divided into five groups: Control, sham operated, ischemia-reperfusion (group IR), losartan without ischemia and losartan with ischemia-reperfusion. The animals underwent 30 min of left anterior descending artery occlusion and subsequent reperfusion for 180 min. The mRNA expression was determined by real time-PCR in ischemic area of the left ventricle (LV) and non ischemic area of right ventricle (RV). Compared to control hearts, exposure to myocardial ischemia-reperfusion produced a significant increase in NOX2 mRNA level in ischemic area of LV (P<0.001) but not in non ischemic area of right ventricle. Although in losartan group, NOX2 mRNA levels neither in LV nor RV were significantly altered, while in losartan and ischemiareperfusion group NOX2 mRNA upregulation in ischemic area was significantly suppressed (P<0.01). Based on the obtained results, it could be concluded that following acute myocardial ischemia– reperfusion, NOX2 mRNA levels were increased in ischemic area of left ventricle but not in non ischemic area of right ventricle, suggesting the local effect of ischemia on the gene expression. Furthermore, inhibition of NOX2 transcription in ischemic area may be a mechanism of the anti ischemia effects of losartan.