title: Possible involvement of nitric oxide synthase in oxidative stress-induced endothelial cell injury.
abstract: The purpose of this study was to characterize the protective effect of NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase, on oxidative stress-induced endothelial cell injury. Intracellular oxidative stress was induced by 1-chloro-2,4-dinitrobenzene, a glutathione (GSH) depleting agent, and the leakage of intracellular lactate dehydrogenase was measured as a marker of cell injury. Addition of 1-chloro-2,4-dinitrobenzene (100-500 microM) induced leakage of lactate dehydrogenase from endothelial cells, and the leakage of lactate dehydrogenase was strongly attenuated by L-NAME, but not by NG-methyl-L-arginine, also an inhibitor of nitric oxide synthase. However, cell injury induced by the Ca2+ ionophore ionomycin was not affected by L-NAME or NG-methyl-L-arginine. Moreover, neither L-NAME nor NG-methyl-L-arginine affected GSH depleting agent-induced or H2O2-induced cell injury in a rat foetal lung fibroblast cell line which lacks nitric oxide synthase. These results suggest that the protective effect of L-NAME is likely to be related to nitric oxide synthase, while the inhibition of nitric oxide production may not be involved in the protective effect of L-NAME, since NG-methyl-L-arginine did not affect endothelial cell injury.
authors.affiliation: Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ishii
authors.forename: T
authors.initials: T
authors.lastname: Yamamoto
authors.forename: S
authors.initials: S
authors.lastname: Shimizu
authors.forename: A
authors.initials: A
authors.lastname: Sano
authors.forename: K
authors.initials: K
authors.lastname: Momose
authors.forename: Y
authors.initials: Y
authors.lastname: Kuroiwa
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology; D002417:Cattle; D004137:Dinitrochlorobenzene / Q000009:adverse effects; D004730:Endothelium, Vascular / Q000201:enzymology / Q000293:injuries*; D005347:Fibroblasts / Q000201:enzymology; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats
chemical_list: D004137:Dinitrochlorobenzene; D007770:L-Lactate Dehydrogenase; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester