NG-硝基-L-精氨酸减轻过氧化氢诱导的内皮细胞损伤。

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

Shimizu S, Nomoto M, Yamamoto T, Momose K

Department of Pharmacology, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.

Br J Pharmacol. 1994 Oct;113(2):564-8. doi: 10.1111/j.1476-5381.1994.tb17026.x.

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. 2. Endothelial cell injury was assessed by measuring the release of intracellular lactate dehydrogenase (LDH) and 51Cr. 3. Addition of H2O2 (250-1,000 microM) 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)-4 x 10(-3) M), L-NOARG (10(-4)-4 x 10(-3) M) and NG-nitro-L-arginine benzyl ester (L-NABE, 10(-4)-4 x 10(-3) M), inhibitors of NO synthase. 4. L-NOARG analogues also reduced H2O2-induced 51Cr release from endothelial cells, while L-NMMA had no effect. 5. The protective effect of L-NAME was not reversed by addition of L-arginine (L-Arg, 1-10 mM). 6. Both L-NAME and L-NMMA completely inhibited L-Arg metabolism to L-citrulline coupled with NO synthesis. 7. 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.

摘要

研究了一氧化氮（NO）合酶抑制剂NG-硝基-L-精氨酸（L-NOARG）和NG-单甲基-L-精氨酸（L-NMMA）的三种类似物对过氧化氢（H2O2）诱导的内皮细胞损伤的影响。2. 通过测量细胞内乳酸脱氢酶（LDH）和51Cr的释放来评估内皮细胞损伤。3. 向内皮细胞中添加H2O2（250-1000 microM）可剂量依赖性地诱导LDH释放。用NO合酶抑制剂NG-硝基-L-精氨酸甲酯（L-NAME，10^(-4)-4×10^(-3) M）、L-NOARG（10^(-4)-4×10^(-3) M）和NG-硝基-L-精氨酸苄酯（L-NABE，10^(-4)-4×10^(-3) M）预处理可减少LDH释放。4. L-NOARG类似物也可减少H2O2诱导的内皮细胞51Cr释放，而L-NMMA则无作用。5. 添加L-精氨酸（L-Arg，1-10 mM）不能逆转L-NAME的保护作用。6. L-NAME和L-NMMA均完全抑制L-Arg代谢为L-瓜氨酸并伴有NO合成。7. 这些发现表明，L-NOARG类似物而非L-NMMA可减少H2O2诱导的内皮细胞损伤，且这些作用可能与抑制NO生成无关。