A nitric oxide donor prevents hydrogen peroxide-mediated endothelial cell injury. Chang, Joon, N. V. Rao, Boaz A. Markewitz, John R. Hoidal, and John R. Michael. Division of Respiratory, Critical Care and Occupational Pulmonary Medicine, Department of Medicine, Veterans Administration Medical Center and the University of Utah School of Medicine, Salt Lake City, Utah and the Pulmonary Division, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
APStracts 3:0014L, 1996.
Since nitric oxide is being used to treat acute lung injury and since 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 [mu]M) prevents the increase in 51Cr release resulting from glucose oxidase or directly applying 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 cGMP analog 8-bromo-cGMP (1-10 mM) does not protect. SNAP decreases in vitro the net oxidation of ferrous to ferric iron by H2O2, the iron-catalyzed consumption of H2O2 in Fenton's reaction, the iron-mediated generation of hydroxyl radicals and the Fe2+-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. 

Received 7 July 1995; accepted in final form 2 January 1996.
APS Manuscript Number L212-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 January 96