Reduction by NG‐nitro‐L‐arginine of H2O2‐induced endothelial cell injury

Abstract

The effects of three analogues of NG‐nitro‐L‐arginine (L‐NOARG) and NG‐monomethyl‐L‐arginine (L‐NMMA), inhibitors of nitric oxide (NO) synthase, on hydrogen peroxide (H2O2)‐induced endothelial cell injury were studied. Endothelial cell injury was assessed by measuring the release of intracellular lactate dehydrogenase (LDH) and 51Cr. Addition of H2O2 (250‐1,000 μm) to endothelial cells induced the release of LDH dose‐dependently. The release of LDH was reduced by pretreatment with NG‐nitro‐L‐arginine methyl ester (L‐NAME, 10−4‐4times 10−3m), L‐NOARG (10−4‐4 × 10−3 m) and NG‐nitro‐L‐arginine benzyl ester (L‐NABE, 10−4‐4times 10−3m), inhibitors of NO synthase. L‐NOARG analogues also reduced H2O2‐induced 51Cr release from endothelial cells, while L‐NMMA had no effect. The protective effect of L‐NAME was not reversed by addition of L‐arginine (L‐Arg, 1‐10mM). Both L‐NAME and L‐NMMA completely inhibited L‐Arg metabolism to L‐citrulline coupled with NO synthesis. These findings suggest that L‐NOARG analogues but not L‐NMMA reduced H2O2‐induced endothelial cell injury, and that these effects may not be related to inhibition of NO production. 1994 British Pharmacological Society