Effect of sodium delivery on superoxide and nitric oxide in the medullary thick ascending limb
Effect of sodium delivery on superoxide and nitric oxide in the medullary thick ascending limb
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DOI：
10.1152/ajprenal.00407.2005
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发表时间：
2006-08-01
影响因子：
4.2
通讯作者：
Cowley, Allen W., Jr.
中科院分区：
文献类型：
--
作者：
Abe, Michiaki;O'Connor, Paul;Cowley, Allen W., Jr.
高血压与氧化应激水平升高和肾髓质损伤相关。先前的研究表明，肾灌注压升高增加了向髓质厚升支（mTAL）的Na+输送，并且在许多高血压实验形式中报告了外髓质中NaCl转运的增强。本研究探讨了在体外灌注的mTAL中增加Na+和液体输送对超氧化物生成的影响。渗透压保持恒定之间的低和高Na+灌注液通过调整胆碱Cl-。实时荧光显微镜技术被用来确定在个别mTAL细胞中使用二氢乙锭和DAF-FM染料，分别产生超氧化物和一氧化氮。将灌注液的Na+浓度从60 mM增加到149 mM或将管腔流速从5 nl/min增加到20 nl/min（固定Na+浓度为60 mM）显著增加了mTAL中超氧化物的产生并降低了一氧化氮。当哇巴因抑制Na+的主动转运时，这些作用被抑制。我们得出结论，增加管腔Na+浓度和/或流速可以增加mTAL中超氧化物的生成，并降低一氧化氮的生物利用度。这可能导致肾髓质血流减少，并在高血压期间促进肾髓质内的缺氧和肾小管坏死。
Hypertension is associated with increased levels of oxidative stress and medullary renal injury. Previous studies have shown that elevations in renal perfusion pressure increase Na+ delivery to the medullary thick ascending limb (mTAL), and enhancement of NaCl transport in the outer medulla has been reported in many experimental forms of hypertension. This study examined the effects of increased Na+ and fluid delivery in mTAL perfused in vitro on the generation of superoxide. Osmolality was maintained constant between low- and high-Na+ perfusates by adjusting with choline Cl-. Real-time fluorescent microscopic techniques were used to determine the generation of superoxide and nitric oxide in individual mTAL cells using dihydroethidium and DAF-FM dyes, respectively. Increasing the Na+ concentration of the perfusate from 60 to 149 mM or luminal flow rate from 5 to 20 nl/min (with fixed Na+ concentration of 60 mM) significantly increased superoxide generation and decreased nitric oxide in mTAL. These effects were inhibited when active transport of Na+ was inhibited by ouabain. We conclude that increases in luminal Na+ concentration and/or flow rate can increase the generation of superoxide in mTAL and reduce nitric oxide bioavailability. This may lead to reduction in medullary blood flow and promote hypoxia and tubular necrosis within the renal medulla during in hypertension.