Study on the protection by nitric oxide generated from L-Arginine

研究了l -精氨酸对大鼠小容量缺氧再氧模型心肌细胞和内皮细胞的保护作用。培养细胞进行90分钟的低容量缺氧和30分钟的再氧合。l -精氨酸（0-0.5 mM）在缺氧前期或再氧合阶段给予。评估一氧化氮（NO）生成、NO合成酶（NOS）活性、cGMP水平和细胞损伤。为了评价l-精氨酸对细胞信号传导的影响，研究了NOS拮抗剂ng -硝基- l-精氨酸甲酯（L-NAME）、No供体s -亚硝基-n -乙酰-青霉胺（SNAP）、鸟苷酸环化酶抑制剂亚甲基蓝、cGMP类似物8-溴-cGMP的作用。这些数据表明，低容量缺氧和再氧化可能增加NOS活性，促进l -精氨酸向NO的转化，从而以剂量依赖的方式保护细胞免受损伤。此外，l -精氨酸的心脏保护作用是通过激活鸟苷酸环化酶实现的，导致大鼠心脏细胞中cGMP水平升高。这一作用涉及一个格列本脲敏感、no - cgmp依赖的途径。

Protective effects of L-arginine were evaluated in a cardiomyocytes and endothels got from rats model of low-volume anoxia and re-oxygenation. Cell cultures were subjected to 90 min of low-volume anoxia and 30 min of re-oxygenation. L-Arginine (0-0.5 mM) was administered during the pre-anoxic period or the re-oxygenation phase. Nitric oxide (NO) production, NO synthase (NOS) activity, cGMP levels, and cellular injury were assessed. To evaluate the effects of the L-arginine on cell signaling, the effects of the NOS antagonist NG-nitro-L-arginine methyl ester (L-NAME), No donor S-nitroso-N-acetyl-penicillamine (SNAP), guanylate cyclase inhibitor methylene blue, cGMP analog 8-bromo-cGMP were examined. This data indicate that low-volume anoxia and re-oxygenation might increase NOS activity and facilitated the conversion of L-arginine to NO, which provided protection against cellular injury in a dose-dependent fashion. In addition, the cardioprotective effects of L-arginine were achived by the activation of guanylate cyclase, leading to increased cGMP levels in rat heart cells. This action involves a glibenclamide-sensitive, NO-cGMP-dependent pathway.