MODULATION OF GLOMERULAR ULTRAFILTRATION COEFFICIENT

肾小球超滤系数，KF或LPA是决定因素之一 肾小球滤过率。建议的长期目标是 调查是为了了解体液、新陈代谢和 控制KF的解剖学机制。在此期间调制KF 生理状态的改变和体液介质的作用。 具体地说，KF在容量耗尽和输液过程中会减少 血管紧张素II和其他血管活性激素的水平，并可能在 容量扩张和输注心钠素后。 KF中的这些变化在体外非灌流肾小球中持续存在，因此 不能仅仅由过滤面积的动态变化引起 系膜细胞收缩。相反，它们最符合 毛细管水力传导性的调制。建议进行的研究 按原样说明KF和LP的调制机制 在没有灌流的情况下观察。既定的学习方法 将使用视频显微镜对分离的肾小球进行过滤。 在过滤过程中毛细管体积的变化将使用 差示干涉对比显微镜。肾小球系膜细胞的作用 收缩对肾小球体积及毛细血管形态和面积的影响 还将使用视频、放射性同位素和形态测量进行评估 技巧。细胞旁通路的详细形态计量学检查 要测试的关于上皮方面的过滤的假设是： 1.系膜收缩改变毛细血管形态，但不改变 影响毛细表面积。肾小球系膜张力由对 几种激素，但独立于LP而变化。2.肾小球 上皮细胞控制LP。LP受体液反应的调节， 当细胞内cAMP水平增加时增加，当细胞内cAMP水平下降时 CGMP水平升高。3.Lp受过滤变化的影响 由上皮足突起变化引起的通路和 过滤缝隙孔。这些变化包括撤回或延长 足突和细胞间通路宽度的变化 紧挨着基底膜。这些研究的结果 研究将使我们能够确定KF和LP的调制是否是一种 与系膜收缩直接相关，或是否如我们所说，LP 随着上皮细胞环核苷酸的不同而变化，并独立于 系膜音调。

Glomerular ultrafiltration coefficient, Kf or LpA, is one determinant of glomerular filtration rate. The long term goal of the proposed investigations is to gain understanding of the humoral, metabolic and anatomic mechanisms responsible for controlling Kf. Kf is modulated during altered physiologic states and by the action of humoral mediators. Specifically, Kf is diminished during volume depletion and during infusion of angiotensin II and other vasoactive hormones and may be increased during volume expansion and following infusion of atrial natriuretic peptide. These variations in Kf persist in vitro in non-perfused glomeruli and thus cannot result solely from dynamic changes in filtration area secondary to mesangial cell contraction. Rather, they are most consistent with modulation of capillary hydraulic conductivity, Lp. The proposed studies address the mechanisms responsible for modulation of Kf and Lp as they are observed in the absence of perfusion. Established methods for studying filtration by isolated glomeruli using videomicroscopy will be used. Changes in capillary volume during filtration will be confirmed using differential interference contrast microscopy. The effects of mesangial contraction on glomerular volume and on capillary configuration and area will also be assessed using video, radioisotope and morphometric techniques. Detailed morphometric examination of the paracellular pathway for filtration on the epithelial aspect of the Hypotheses to be tested are: 1. Mesangial contraction changes capillary configuration and does not affect capillary surface area. Mesangial tone is altered by responses to several hormones but varies independently from Lp. 2. Glomerular epithelial cells control Lp. Lp is modulated by humoral responses and increases when intracellular levels of cAMP increase and decreases when levels of cGMP increase. 3. Lp is modulated by changes in the filtration pathway that result from changes in epithelial foot processes and the filtration slit-pore. These changes include retraction or extension of the foot processes and changes in the width of the intercellular pathway immediately adjacent to the basement membrane. The results of these studies will enable us to determine whether modulation of Kf and Lp is a direct correlate of mesangial contraction or whether, as we propose, Lp varies with epithelial cell cyclic nucleotides and is independent of mesangial tone.