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

L-精氨酸产生的一氧化氮的保护作用研究

• 批准号: 13671394
• 负责人: NONAMI Yoshiki
• 金额: $ 0.64万
• 依托单位: Kochi University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671394/
• 关键词: cardiomyocytes; endothels; L-Arginine; nitric oxide

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.

采用大鼠低容量缺氧复氧模型，观察L精氨酸对心肌细胞和血管内皮细胞的保护作用。培养的细胞接受90min的低容量缺氧和30min的复氧。在缺氧前或复氧期给予L-精氨酸(0~0.5 mM)。检测一氧化氮(NO)生成、一氧化氮合酶(NOS)活性、cGMP水平及细胞损伤情况。观察了一氧化氮合酶拮抗剂L精氨酸甲酯、一氧化氮供体S亚硝基-N-乙酰青霉胺、鸟苷环化酶抑制剂亚甲蓝、环鸟苷类似物8-溴-环鸟苷对细胞信号转导的影响，以探讨精氨酸对细胞信号转导的影响。提示低剂量缺氧和复氧可增加一氧化氮合酶活性，促进L精氨酸转化为一氧化氮，对细胞损伤具有保护作用，且呈剂量依赖关系。此外，L-精氨酸的心脏保护作用是通过激活鸟苷环化酶，导致大鼠心肌细胞内cGMP水平升高而实现的。这一作用涉及格列本脲敏感、NO-cGMP依赖的途径。

项目成果

Nitric oxide generated from L-Arginine protects cardiomyocytes and endothels from reperfusion injury produced by hypoxia and re-oxygenation.

L-精氨酸产生的一氧化氮可保护心肌细胞和内皮细胞免受缺氧和再氧合引起的再灌注损伤。

• 期刊: J Cardiac Failure (in press)
• 作者: Nonami Y;Shiono N;Sasaguri S
• 通讯作者: Sasaguri S