肾脏是体内N^G-D-硝基精氨酸单向手性转化的主要器官  被引量:4

Kidney is the main organ on N^G-nitro-D-arginine chiral inversion in rats

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作  者:辛艳飞[1] 程熹[1] 王广基[2] 周向军[1] 王永祥[1] 

机构地区:[1]上海交通大学药学院分子药理实验室,上海200030 [2]中国药科大学江苏省药物代谢动力学重点实验室,江苏南京210009

出  处:《中国药理学通报》2004年第9期989-993,共5页Chinese Pharmacological Bulletin

基  金:科技部国家"十五"科技攻关专项基金资助项目 ;No2 0 0 3AA 2Z 3 47A

摘  要:目的 研究NG D 硝基精氨酸 (NG nitro D arginine,D NNA)在体内发生手性转化的的部位。方法 考察肾脏结扎对于D NNA诱导大鼠动脉压升高活性的变化 ,并运用毛细管电色谱 (capillaryelectrochromatography ,CEC)分析技术测定D NNA在体内手性转化的情况。结果 肾脏结扎使大鼠完全丧失对D NNA (32mg·kg-1)升高血压反应 ,但不影响由NG L 硝基精氨酸 (NG nitro L arginine ,L NNA)(16mg·kg-1)引起的升压反应。而D NNA/肾匀浆孵育液(32mg·kg-1)则可使肾脏结扎大鼠产生升压反应。CEC血药检测证实D NNA在大鼠体内转化生成L NNA ,而L NNA在体内未被代谢生成D NNA ;肾脏结扎则使D NNA的手性转化大量减少。结论 D NNA在大鼠体内可单向代谢转化L NNA ,肾脏是DAim To investigate metabolism and chiral inversion of N G-nitro-D-arginine (D-NNA) in vivo. Methods The change on mean arterial pressure (MAP) in kidney-ligated rats or sham-operated rats was observed.Plasma concentrations of both L-NNA and D-NNA at 1 h after iv. bolus injection of D-NNA or L-NNA respectively were measured by capillary electrochromatography (CEC) .Results Bilateral kidn-eyligation abolished the pressor response to iv bolus injection of D NNA (32mg·kg- 1)but not to L NNA (16mg·kg- 1) in rats.Kidney homogenates in cubated with D NNA (32mg·kg- 1) ,however ,pro duced pressor response in kidney ligated rats .CEC detection showed D NNA can be converted to L NNA but no L NNA to D NNA in sham operated rats .Moreover ,L NNA concent ration was much re duced in kidney ligated rats compared with that in controlrats .Conclusion These results indicate that D NNA can be unidirection ally converted to L NNA and the kidney is the primary organ on D NNA chiral inversion .

关 键 词:D-NNA L-NNA 手性转化 肾脏 

分 类 号:R-332[医药卫生] R322.61

 

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