L-Arginine Enhances Nitrative Stress and Exacerbates Tumor Necrosis Factor-α Toxicity to Human Endothelial Cells in Culture: Prevention by Propofol

• DOI: 10.1097/fjc.0b013e3181d265a3
• Publication Date: 2010-03-26T09:42:01Z
• Authors: Zhengyuan Xia; Tao Luo; Hui-min Liu; Fang Wang; Zhong-yuan Xia; Michael G Irwin; Paul M Vanhoutte
• Keywords: Nitrotyrosine; Peroxynitrous acid

Supplementation of L-arginine, a nitric oxide precursor, during the late phase myocardial ischemia/reperfusion increases myocyte apoptosis and exacerbates injury, but underlying mechanism is unclear. During ischemia/reperfusion, endothelial cells precedes that cardiomyocyte. Tumor necrosis factor-α (TNF) production increased which may exacerbate injury by inducing cell apoptosis. We postulated L-arginine TNF-induced enhancing peroxynitrite-mediated nitrative stress. Cultured human umbilical vein were either not treated (control) or with TNF alone in presence nonselective synthase inhibitor N (omega)-nitro-L-arginine (L-NNA), propofol (an anesthetic scavenges peroxynitrite), plus propofol, respectively, for 24 hours. intracellular superoxide hydrogen peroxide accompanied inducible (iNOS) protein expression production. This was nitrotyrosine, fingerprint peroxynitrite an index stress, did enhance further increase nitrotyrosine exacerbated TNF-mediated L-NNA reduced stress attenuated cellular toxicity. The L-arginine-mediated enhancement toxicity propofol. Thus, under pathological conditions associated production, supplementation