Safari F, Hajiadeh S, Moshtaghion S H, Forouzandeh Moghadam M, Shekarforoush S, Bayat G, et al . Effect of losartan on NOX2 transcription following acute myocardial ischemia-reperfusion. Physiol Pharmacol 2012; 16 (1) :44-53
URL:
http://ppj.phypha.ir/article-1-803-en.html
Abstract: (11565 Views)
Introduction: 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.
Methods: 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).
Results: 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).
Conclusion: 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.