Igarashi J, Nishida M, Hoshida S, Yamashita N, Kosaka H, Hori M, Kuzuya T, Tada M
Department of Pathophysiology, Osaka University Medical School, Japan.
Am J Physiol. 1998 Jan;274(1):C245-52. doi: 10.1152/ajpcell.1998.274.1.C245.
The effects of nitric oxide (NO) produced by cardiac inducible NO synthase (iNOS) on myocardial injury after oxidative stress were examined: Interleukin-1 beta induced cultured rat neonatal cardiac myocytes to express iNOS. After induction of iNOS, L-arginine enhanced NO production in a concentration-dependent manner. Glutathione peroxidase (GPX) activity in myocytes was attenuated by elevated iNOS activity and by an NO donor, S-nitroso-N-acetyl-penicillamine (SNAP). Although NO production by iNOS did not induce myocardial injury, NO augmented release of lactate dehydrogenase from myocyte cultures after addition of H2O2 (0.1 mM, 1 h). Inhibition of iNOS with N omega-nitro-L-arginine methyl ester ameliorated the effects of NO-enhancing treatments on myocardial injury and GPX activity. SNAP augmented the myocardial injury induced by H2O2. Inhibition of GPX activity with antisense oligodeoxyribonucleotide for GPX mRNA increased myocardial injury by H2O2. Results suggest that the induction of cardiac iNOS promotes myocardial injury due to oxidative stress via inactivation of the intrinsic antioxidant enzyme, GPX.
研究了心脏诱导型一氧化氮合酶（iNOS）产生的一氧化氮（NO）对氧化应激后心肌损伤的影响：白细胞介素-1β诱导培养的大鼠新生心肌细胞表达iNOS。iNOS诱导后，L-精氨酸以浓度依赖的方式增强NO的产生。iNOS活性升高以及NO供体S-亚硝基-N-乙酰青霉胺（SNAP）可减弱心肌细胞中的谷胱甘肽过氧化物酶（GPX）活性。虽然iNOS产生的NO不会诱导心肌损伤，但在加入H2O2（0.1 mM，1小时）后，NO会增加心肌细胞培养物中乳酸脱氢酶的释放。用Nω-硝基-L-精氨酸甲酯抑制iNOS可改善NO增强处理对心肌损伤和GPX活性的影响。SNAP增强了H2O2诱导的心肌损伤。用针对GPX mRNA的反义寡脱氧核糖核苷酸抑制GPX活性会增加H2O2诱导的心肌损伤。结果表明，心脏iNOS的诱导通过使内源性抗氧化酶GPX失活，促进氧化应激导致的心肌损伤。
