ROLE OF ENDOTHELIUM IN GLOMERULAR DYSFUNCTION

既往对急性肾衰竭的研究已描述了 调节肾循环内的血管张力，范围从 持续性血管收缩导致血管反应异常 血管扩张剂和血管收缩剂的数量。 在很大程度上， 观察结果仍然没有进一步的解释机制。 中的感兴趣 这方面的新信息表明， 细胞精心制作强大的血管舒张（内皮衍生的松弛 因子，EDRF）和血管收缩（内皮素）物质， 调节局部血管张力、局部血流，在肾脏中， 调节肾小球滤过过程的潜力。 迄今为止收集的初步数据支持EDRF和 和内皮素在调节肾循环和GFR中的作用。 研究 将在Munich-Wistar大鼠中进行，其肾损伤继发于 缺血/再灌注，暴露于内毒素和活化的多形核细胞 白细胞 拟议的项目包括一项新开发的技术 它允许对肾脏的一部分进行实验操作： 主肾动脉的分支（内皮素，内皮素抗体， 内毒素等）。 微穿刺技术可以比较血液动力学和 形态学技术可以比较操作中的结构变化， 以及肾脏内的未操纵的肾小球/脉管系统。 具体目标包括： 1)对内皮细胞作用的生理学评估 细胞 几种急性肾血流动力学异常 肾衰竭和 活性氧在其中作用 现象 2)肾微循环内的形态学评估， 外源性/内源性内皮素。 3)内皮衍生物质调节的评估 测量正常和受损肾脏中的生化标志物， 肾小球 和系膜细胞。 4)血浆内皮素和其他生理指标的评估 流体 内皮细胞受损的情况。 5)肾损伤后肾小球内皮素受体的变化 肾脏

Previous investigations of acute renal failure have described impairment in regulation of vasomotor tone within the renal circulation, ranging from persistent vasoconstriction to abnormalities in the vascular response to a number of vasodilators and vasoconstrictors. In large part these observations remain without further explanatory mechanisms. Of interest in this regard is the explosion of new information indicating that endothelial cells elaborate powerful vasodilating (endothelium-derived relaxation factor, EDRF) and vasoconstricting (endothelin) substances which can regulate local vascular tone, regional blood flow and, in the kidney, the potential to modulate the process of glomerular filtration. Preliminary data collected thus far, support important roles for both EDRF and endothelin in modulating the renal circulation and GFR. The studies will be performed in Munich-Wistar rats with renal injury secondary to ischemia/reperfusion, exposure to endotoxin and activated polymorphonuclear leukocytes. The proposed projects include a newly developed technique which allows experimental manipulations of portions of a kidney: infusion of a branch of the main renal artery (endothelin, endothelin antibody, endotoxin etc). Micropuncture techniques can compare hemodynamics and morphological techniques can compare the structural changes in manipulated and non manipulated glomeruli/vasculature within that kidney. The specific aims include: 1) Physiologic assessment of the contribution of endothelial cells to abnormal renal hemodynamics in several forms of acute renal failure and the role of reactive oxygen species in these phenomenon. 2) Morphological assessment within the renal microcirculation to exogenous/endogenous endothelin. 3) Assessment of modulation by endothelium-derived substances by measuring biochemical markers in normal and injured kidneys, glomeruli and mesangial cells. 4) Assessment of endothelin in plasma and other physiologic fluids in conditions having injured endothelial cells. 5) Characterization of glomerular endothelin receptors in injured kidneys.