ROLE OF ENDOTHELIUM IN GLOMERULAR DYSFUNCTION

以前对急性肾功能衰竭的研究已经描述了 调节肾循环内的血管运动张力，范围从 对血管反应异常的持续性血管收缩 血管扩张剂和缩血管药的数量。其中很大一部分是 观察结果仍然没有进一步的解释机制。感兴趣的人 这方面的新信息爆炸式增长，表明内皮细胞 细胞精心设计强大的血管扩张(内皮源性松弛 因子，EDRF)和血管收缩(内皮素)物质，可以 调节局部血管张力，局部血流，在肾脏， 有可能调节肾小球滤过的过程。 到目前为止收集的初步数据支持两个EDRF的重要作用 内皮素在调节肾循环和肾小球滤过率中的作用。这些研究 将在继发性肾损伤的慕尼黑-Wistar大鼠身上进行 缺血/再灌注、内毒素暴露与中性粒细胞活化 白细胞。提议的项目包括一项新开发的技术 允许对肾脏部分进行实验性操作的方法：输液 主要肾动脉的一个分支(内皮素、内皮素抗体、 内毒素等)。微穿刺术可以比较血流动力学和 形态技术可以比较操控后的结构变化 以及肾脏内未被操控的肾小球/血管系统。 具体目标包括： 1)对内皮细胞的贡献进行生理学评估 几种形式的急性肾功能衰竭和肾脏血流动力学异常 活性氧物种在这些现象中的作用。 2)肾微循环内的形态评估 外源性/内源性内皮素。 3)评估内皮衍生物质的调节作用 正常和受损肾脏、肾小球生化标志物的测定 和系膜细胞。 4)血浆和其他生理液中内皮素的测定 内皮细胞受损的情况。 5)损伤后肾小球内皮素受体的变化特征 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.