ULTRAFILTRATION CHARACTERISTICS OF ISOLATED GLOMERULI

在进行拟议的研究时，我们会继续研究 分离的哺乳动物肾小球的超滤特性 更好地了解决定肾小球的机制 正常和病理状态下的滤过。在过去的三年里， 我们开发了分离完整肾小球和诱导 体外过滤，估计过滤速度，超滤 肾小球系数(LPA)、肾小球细胞和细胞外体积 顺应性和耐灌注性。我们测量了肾小球的LPA 正常的老鼠、兔子、狗、羊和人类。我们已经记录了 各物种LPA随肾小球大小的增加而增加，随肾小球大小的增加而减少 在容量耗竭期间以及在已建立的缺血和毒性损伤中。我们 将继续改进我们估计LPA的方法，通过改变 用于生产的孵化条件、致癌剂和梯度 过滤。我们将研究肾小球细胞与 基底膜的形态和过滤，并试图定义 内皮细胞窗总面积改变的影响， 基底膜和上皮裂隔膜。我们将调查 血管活性物质及其拮抗剂对肾小球的影响 使用体内给药或添加到孵化中的药物起作用 体外培养。我们还将扩大我们的研究范围，将正常肾小球包括在内。 人体肾脏和肾活检标本。我们预计这些研究 将有助于更好地理解肾小球滤过的过程 以及它被调节的机制。这种理解可能会在以后 允许对人类肾功能不全进行合理干预。

In conducting the proposed research we will continue to study the intrinsic ultrafiltration characteristics of isolated mammalian glomeruli in order to achieve a better understanding of the mechanisms which determine glomerular filtration in normal and pathologic states. During the past three years, we developed techniques for isolating intact glomeruli and inducing filtration in vitro, estimating filtration rate, ultrafiltration coefficient (LpA), glomerular cell and extracellular volume, glomerular compliance and resistance to perfusion. We have measured LpA of glomeruli of normal rats, rabbits, dog, sheep and humans. We have documented that LpA increases with increasing glomerular size in each species and decreases during volume depletion and in established ischemic and toxic injury. We will continue to refine our methods for estimating LpA by varying incubation conditions, oncotic agents and gradients used to produce filtration. We will study correlations between glomerular cell and basement membrane morphology and filtration and attempt to define the effects of alterations in total area of endothelial cell fenestrae, basement membrane and epithelial slit diaphragms. We will investigate the effects of vasoactive substances and their antagonists on glomerular function using agents administered in vivo or added to the incubation in vitro. We will also extend our studies to include glomeruli from normal human kidneys and renal biopsy specimens. We anticipate that these studies will lead to a better understanding of the process of glomerular filtration and the mechanisms by which it is modulated. This understanding may later permit rational intervention in human renal insufficiency.