title: The opposite roles of nNOS in cardiac ischemia-reperfusion-induced injury and in ischemia preconditioning-induced cardioprotection in mice.
abstract: The role of neuronal nitric oxide synthase (nNOS) in cardiac ischemia-reperfusion (IR) and ischemia preconditioning (IP) is still controversial. Here, we focused on the possible roles of nNOS in cardiac IR and IP. Wild type C57BL/6 (WT) mice were subjected to coronary artery occlusion for 30 min followed by 24-h reperfusion (IR). Cardiac injury (infarct size and apoptotic cell number) was increased, associated with elevation of oxidative stress (lipid peroxidation) and nitrative stress (nitrotyrosine formation). A potent nNOS inhibitor, L-VNIO, and a superoxide dismutase mimetic and peroxynitrite scavenger, MnTBAP, significantly reduced IR-induced increases of oxidative/nitrative stress and cardiac injury. IR-induced cardiac injury in nNOS(-/-) (KO) mice was significantly lower than that in WT mice. MnTBAP markedly reduced IR-induced cardiac injury by suppression of oxidative/nitrative stress in KO mice. Cardiac IP was performed by three cycles of 5-min IR before 30-min ischemia followed by 24-h reperfusion. IP attenuated IR-induced cardiac injury in WT mice associated with reductions of oxidative/nitrative stress. IP-induced reduction of cardiac injury and oxidative/nitrative stress were eliminated by pretreatment with L-VNIO. In contrast with WT mice, IP had no protective effects in nNOS KO mice. In conclusion, nNOS played a dual role during cardiac IR and IP; nNOS exacerbated IR-induced injury by increasing oxidative/nitrative stress and contributed to IP-induced protection by inhibition of oxidative/nitrative stress.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Kagawa University, Takamatsu 761-0793, Japan.
authors.forename: Xiao-Mei
authors.initials: XM
authors.lastname: Lu
authors.forename: Guo-Xing
authors.initials: GX
authors.lastname: Zhang
authors.forename: Yan-Qiu
authors.initials: YQ
authors.lastname: Yu
authors.forename: Shoji
authors.initials: S
authors.lastname: Kimura
authors.forename: Akira
authors.initials: A
authors.lastname: Nishiyama
authors.forename: Hiroko
authors.initials: H
authors.lastname: Matsuyoshi
authors.forename: Juichiro
authors.initials: J
authors.lastname: Shimizu
authors.forename: Miyako
authors.initials: M
authors.lastname: Takaki