Early stage of obesity potentiates nitric oxide reduction during the development of renal failure
Early stage of obesity potentiates nitric oxide reduction during the development of renal failure
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DOI：
10.1007/s40620-013-0029-9
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发表时间：
2014-06-01
影响因子：
3.4
通讯作者：
Escalante, Bruno
中科院分区：
文献类型：
--
作者：
Maria Gamez-Mendez, Ana;Vargas-Robles, Hilda;Escalante, Bruno
背景肥胖是一种严重的健康问题，与多种代谢性疾病的发病机制有关。一氧化氮（NO）在肾功能中起重要作用，并且NO水平的改变与肥胖的发病机制有关。因此，我们的目的是研究是否肥胖的早期阶段有助于肾功能衰竭的进展，通过进一步的NO impairment.Methods雄性C57 BL/6小鼠喂食高脂饮食（HFD）或正常饮食（ND）在2周。所有小鼠均接受假手术（sham）或5/6肾切除术（Np）。一组HFD Np小鼠用抗氧化剂加L-精氨酸处理。肾损伤参数进行了评估和eNOS代谢evaluated.Results小鼠的体重增加，eNOS蛋白和mRNA的表达，和自由基氧（ROS）。尿亚硝酸盐排泄、尿量和血浆BH 4减少。在HFD小鼠中，5/6 Np进一步增加BH 2和尿蛋白浓度、ROS水平和eNOS mRNA表达。BH 4血浆水平和尿亚硝酸盐排泄量的下降加剧。NO合成刺激与抗氧化剂+L-精氨酸治疗阻止了所有这些changes.Conclusions NO代谢的早期变化与早期阶段的肥胖。这种对NO的作用增强了肾损伤的发展。
Background Obesity is a serious health problem associated with the pathogenesis of various metabolic diseases. Nitric Oxide (NO) plays an important role in kidney function and altered NO levels have been associated with the pathogenesis of obesity. Therefore, we aimed to study whether an early stage of obesity contributes with progression of renal failure through further NO impairment.Methods Male C57BL/6 mice were fed with a high-fat diet (HFD) or a normal diet (ND) during 2 weeks. All mice underwent either sham surgery (sham) or 5/6 nephrectomy (Np). One group of HFD Np mice was treated with antioxidants plus L-arginine. Kidney damage parameters were assessed and eNOS metabolism was evaluated.Results Mice on a HFD increased body weight, eNOS protein and mRNA expression, and radical oxygen species (ROS). Urine nitrites excretion, urine volume, and plasma BH4 were decreased. In HFD mice, 5/6 Np further increased BH2 and urine protein concentration, ROS levels, and eNOS mRNA expression. The decrease in BH4 plasma levels and urine nitrites excretion was accentuated. NO synthesis stimulation with the antioxidants + L-arginine treatment prevented all these changes.Conclusions The early changes in NO metabolism are associated with an early stage of obesity. This effect on NO potentiates kidney damage development.