title: Valsartan attenuates oxidative stress and NF-κB activation and reduces myocardial apoptosis after ischemia and reperfusion.
abstract: Myocardial apoptosis is primarily triggered during reperfusion. Various mechanisms are involved, including oxidative stress which activates the translocation of nuclear factor-kappa B (NF-κB) and stimulates the release of tumor necrosis factor-alpha (TNF-α). However, the relative contribution of the renin angiotensin system (RAS) to the development of myocardial apoptosis during reperfusion remains unknown. In the present study, we examined whether inhibition of RAS with Valsartan, an Angiotensin II 1 receptor (AT1) antagonist, could reduce apoptosis during reperfusion. We constructed a rat model of myocardial ischemia reperfusion injury. Rats were pretreated with Valsartan for 2 weeks, and then subjected to 30 min ischemia and 4h reperfusion. Apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Levels of malondialdehyde (MDA), superoxide dismutase (SOD), TNF-α, and caspase-3 were detected by ELISA. NF-κB, Nicotinamide Adenine Dinucleotide Phosphate (NADPH) oxidase expression was assessed by Western blot analysis. Valsartan inhibited apoptosis (TUNEL staining) in ischemic myocardium (P<0.05), consistent with reduced caspase-3 activity. Valsartan also inhibited of NF-κB translocation to nucleus (P<0.05), and decreased plasma TNF-α levels (P<0.05). Valsartan pretreatment suppressed MDA content and preserved SOD activity, consistent with reduced NADPH oxidase expression (P<0.01). These data provided substantial evidence that RAS was involved in NF-κB activation, mediated by AT1 dependent oxidative stress; thus, RAS might ultimately promote myocardial apoptosis during reperfusion pathogenesis.
authors.affiliation: Department of Cardiology, First Hospital of Quanzhou Affiliated to Fujian Medical University, 250 East Street, Quanzhou 362000, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Wu
authors.forename: Rong
authors.initials: R
authors.lastname: Lin
authors.forename: Ruozhu
authors.initials: R
authors.lastname: Dai
authors.forename: Chengbo
authors.initials: C
authors.lastname: Chen
authors.forename: Haiyun
authors.initials: H
authors.lastname: Wu
authors.forename: Meiman
authors.initials: M
authors.lastname: Hong
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D019255:NADPH Oxidases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000097:blood; D013777:Tetrazoles / Q000494:pharmacology* / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000068756:Valsartan
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D016328:NF-kappa B; D013777:Tetrazoles; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D000068756:Valsartan; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; D053148:Caspase 3; D014633:Valine