title: Role of neuronal nitric oxide synthase in the cardiac ischemia reperfusion in mice.
abstract: Several studies have demonstrated the role of endothelial and inducible nitric oxide synthase in cardiac ischemia reperfusion(IR). However, the role of neuronal nitric oxide synthase (nNOS) in IR is still controversial. The present study was designed to explore the possible involvement of nNOS in cardiac IR. nNOS-/- knockout (KO) and wild type C57 (WT) mice were subjected to 45 min of ischemia by left descending branch of coronary artery ligation followed by 3 h reperfusion, which plasma was collected for creatine kinase (CK) and lactate dehydrogenase (LDH) measurements, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining and measurements of activities of caspase-3, -8, -9, phospho-p38, -ERK, -JNK mitogen-activated protein kinase (MAPK) and phospho-nNOS, phospho-eNOS and iNOS. IR induced cardiac tissue apoptosis by increases of TUNEL staining and activities of caspase-3, -8, and -9, accompanied with increase of CK and LDH concentration and phosphorylation of p38, ERK and JNK MAPK and phospho-nNOS, phospho-eNOS and iNOS in both mouse strains. However, IR induced increases of TUNEL staining and activities of caspase-3, -8 and -9, and CK and LDH concentrations and activation of p38 MAPK were markedly lower in KO mice compared with WT mice. But the phosphorylation of eNOS was significantly higher compared with WT IR group (P < 0.05). The data obtained suggest that nNOS exacerbates IR-induced injury maybe involving p38 MAPK activation.
authors.affiliation: Department of Pathophysiology, College of Basic Medical Sciences, China Medical University Shenyang 110001, Liaoning, People's Republic of China.
authors.forename: Xiao-Mei
authors.initials: XM
authors.lastname: Lu
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.forename: Hai-Peng
authors.initials: HP
authors.lastname: Zhang
mesh_terms: D000818:Animals; D003402:Creatine Kinase / Q000097:blood; D004789:Enzyme Activation; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000201:enzymology*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*
chemical_list: D007770:L-Lactate Dehydrogenase; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; D020928:Mitogen-Activated Protein Kinases; D003402:Creatine Kinase