High glucose augments arginase activity and nitric oxide production in the renal cortex.
High glucose augments arginase activity and nitric oxide production in the renal cortex.
复制标题
高葡萄糖会增强肾皮质中精氨酸酶的活性和一氧化氮的产生。
DOI：
10.1016/j.metabol.2004.02.011
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Suga,Tetsuya
中科院分区：
文献类型：
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作者：
Ishii,Naohito;Ikenaga,Hideki;Carmines,PamelaK;Aoki,Yoshikazu;Ogawa,Zensuke;Saruta,Takao;Suga,Tetsuya
为了阐明正常和高葡萄糖水平下肾脏中精氨酸酶和一氧化氮 (NO) 产生之间的相互作用，将雄性 Sprague-Dawley 大鼠的肾皮质切片在含有不同浓度的 l-正缬氨酸（Nval；一种精氨酸酶抑制剂）、500 U/mL 超氧化物歧化酶以及 5 mmol/L（正常）或 20 mmol/L 的 Hank 溶液中孵育。 （高）葡萄糖（每组 n = 5）。与 Nval 一起孵育会增加肾皮质 NOX（亚硝酸盐 + 硝酸盐）的产生，呈剂量依赖性，表明精氨酸酶和 NO 合酶 (NOS) 之间对底物（L-精氨酸）的竞争。在没有 Nval 的基础条件下，高葡萄糖也会将 NOX 生成量增加到正常葡萄糖孵育期间观察到的速率的 3 倍 (P < .01)。 Nval 不会改变高葡萄糖的这种影响。相反，高葡萄糖和 Nval 的作用是相加的，表明高葡萄糖增强了 NOS 本身的活性。精氨酸酶和 NOS 活性的直接测定证实了两种酶在高葡萄糖条件下受到刺激（分别与正常葡萄糖相比，P < .05、P < .01）。然而，高葡萄糖并没有改变肾皮质切片中存在的 L-精氨酸的量。这些数据表明精氨酸酶在肾皮质中与 NOS 竞争 L-精氨酸，并且高葡萄糖会增加两种酶的活性而不影响底物的量。这些结果表明，NOS 活性的增加，而不是底物可用性的改变，可能是糖尿病肾脏中 NO 合成增加的主要因素。
To clarify the interaction between arginase and nitric oxide (NO) production in the kidney with normal and high glucose levels, renal cortical slices from male Sprague-Dawley rats were incubated in Hank’s solution containing various concentrations of l-norvaline (Nval; an arginase inhibitor), 500 U/mL superoxide dismutase, and either 5 mmol/L (normal) or 20 mmol/L (high) glucose (n = 5 per group). Incubation with Nval increased renal cortical NOX(nitrite + nitrate) production dose-dependently, indicating competition between arginase and NO synthase (NOS) for the substrate (l-arginine). In the basal condition without Nval, high glucose also increased NOXproduction to a rate 3 times that observed during incubation with normal glucose (P < .01). This effect of high glucose was not altered by Nval. Rather, the effects of high glucose and Nval were additive, indicating that the activity of NOS per se is enhanced by high glucose. Direct assay of arginase and NOS activities confirmed stimulation of both enzymes under the high glucose condition (P < .05, P < .01, v normal glucose, respectively). However, high glucose did not change the amount of l-arginine present in renal cortical slices. These data reveal that arginase competes with NOS for l-arginine in the renal cortex, and that high glucose increases the activity of both enzymes without affecting the amount of substrate. These results suggest that increased NOS activity, rather than altered substrate availability, may be the principal factor underlying increased NO synthesis in diabetic kidneys.