Nitric oxide donor prevents hydrogen peroxide-mediated endothelial cell injury.
Because nitric oxide is being used to treat acute lung injury and because it may either reduce or potentiate oxidant-mediated vascular injury, we studied the effect of the nitric oxide donor S-nitroso-N-acetyl-D-penicillamine (SNAP) on hydrogen peroxide (H2O2)-induced injury to cultured rat lung microvascular endothelial cells (RLMVC). Cells were exposed to H2O2 through its enzymatic generation by glucose and glucose oxidase or by its direct application. Glucose oxidase exposure causes a concentration- and time-dependent increase in 51chromium (51Cr) release from RLMVC. Catalase, dimethylthiourea or deferoxamine protects against this oxidant injury. SNAP (100 microM) prevents the increase in 51Cr release resulting from glucose oxidase or direct application of H2O2. N-acetyl-D-penicillamine is ineffective. Photo-decayed SNAP slightly decreases the 51Cr release caused by glucose oxidase but not the injury produced by directly adding H2O2. Treatment with the guanosine 3',5'-cyclic monophosphate (cGMP) analogue 8-BrcGMP (1-10 mM) provides no protection. SNAP decreases in vitro the net oxidation of ferrous to fcrric iron by H2O2, the iron-catalyzed consumption of H2O2 in Fenton's reaction, the iron-mediated generation of hydroxyl radicals, and the Fe(2+)-H2O2-catalyzed peroxidation of lipid membranes. Providing exogenous nitric oxide dramatically prevents H2O2-mediated endothelial injury, likely by reducing iron-mediated oxidant generation and subsequent lipid peroxidation.
Chang
J
J
Department of Medicine, Veterans Affairs Medical Center, Salt Lake City, Utah 84132, USA.
Rao
N V
NV
Markewitz
B A
BA
Hoidal
J R
JR
Michael
J R
JR
D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects*; D005949:Glucose Oxidase / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008833:Microcirculation / Q000187:drug effects; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects*; D051381:Rats; D026423:S-Nitroso-N-Acetylpenicillamine
D026423:S-Nitroso-N-Acetylpenicillamine; D006861:Hydrogen Peroxide; D005949:Glucose Oxidase; D010396:Penicillamine