ULTRAFILTRATION CHARACTERISTICS OF ISOLATED GLOMERULI

在进行拟议的研究时，我们将继续研究 分离的哺乳动物肾小球的超滤特性， 更好地理解决定肾小球疾病的机制， 正常和病理状态下的过滤。 在过去的三年里， 我们开发了分离完整肾小球并诱导 体外滤过，估计滤过率，超滤 系数（LpA），肾小球细胞和细胞外容积，肾小球 顺应性和灌注阻力。 测定肾小球LpA 正常的老鼠、兔子、狗、羊和人类。 我们已经记录了 在每个物种中，LpA随着肾小球大小的增加而增加， 在血容量不足和确定的缺血性和毒性损伤中。 我们 我将继续改进我们的方法，估计LpA的变化， 孵育条件、孵育剂和梯度 过滤 我们将研究肾小球细胞和 基底膜形态和过滤，并试图定义 内皮细胞窗孔总面积改变的影响， 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作用 使用体内施用的或加入到孵育中的试剂， 体外 我们还将扩大我们的研究，包括肾小球从正常 人类肾脏和肾活检标本。 我们预计这些研究 将有助于更好地了解肾小球滤过过程 以及调节它的机制。 这一认识可能以后 允许合理干预人类肾功能不全。

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.