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Selective stimulation of L-arginine uptake contributes to shear stress-induced formation of nitric oxide.

机译:L-精氨酸摄取的选择性刺激有助于剪切应力诱导的一氧化氮的形成。

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The aim of this study was to investigate the kinetics of L-arginine transport mechanisms and the role of extracellular L-arginine in nitric oxide formation during shear stress activation of endothelial cells. Porcine aortic endothelial cells were grown to confluence and were exposed to various amounts of shear stress for 40 min. Formation of nitric oxide was monitored by measuring elevation of endothelial cGMP. Activity of amino acid transport systems was determined by measuring the uptake of L-[3H]leucine (L system) and L-[3H]arginine (y+) under resting and shear stress condition. Shear stress-mediated nitric oxide formation critically depended on the presence of extracellular L-arginine, which increased shear stress-induced cGMP increases in a concentration dependent manner (EC50=123 microM). In addition, shear stress increased L-arginine uptake, while the transport capacity for neutral amino acids (L system) remained unchanged under shear stress conditions. Analysis of the kinetics of the uptake of L-arginine under resting and shear stress conditions indicate that shear stress increased velocity of the high affinity, low capacity transport (y+) without affecting affinity of this system. These data suggest that shear stress selectively activates uptake of L-arginine in endothelial cells and that the uptake of L-arginine might be important for shear stress-mediated nitric oxide formation.
机译:本研究的目的是研究内皮细胞剪切应力激活过程中L-精氨酸转运机制的动力学以及细胞外L-精氨酸在一氧化氮形成中的作用。猪主动脉内皮细胞生长至汇合,并暴露于各种剪切应力下40分钟。通过测量内皮cGMP的升高来监测一氧化氮的形成。氨基酸转运系统的活性通过在静止和剪切应力条件下测量L- [3H]亮氨酸(L系统)和L- [3H]精氨酸(y +)的吸收来确定。剪切应力介导的一氧化氮形成关键取决于细胞外L-精氨酸的存在,其以浓度依赖性方式(EC50 = 123 microM)增加了剪切应力诱导的cGMP的增加。另外,剪切应力增加了L-精氨酸的摄取,而在剪切应力条件下中性氨基酸(L系统)的转运能力保持不变。在静止和剪切应力条件下摄取L-精氨酸的动力学分析表明,剪切应力增加了高亲和力,低容量转运(y +)的速度,而不影响该系统的亲和力。这些数据表明剪切应力选择性地激活内皮细胞中L-精氨酸的摄取,并且L-精氨酸的摄取对于剪切应力介导的一氧化氮形成可能是重要的。

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