AUTOREGULATION OF GLOMERULAR FILTRATION RATE

正常的肾功能需要肾小球的密切配合 过滤和管子重吸收，以防止大的摆动 卷状态。这种协调在很大程度上是由以下过程调节的 肾小球小管平衡(GTB)--肾小管的血流依赖性 重吸收和肾小管球反馈(TGF)，这是阴性的 近端晚期对肾单位滤过率的反馈调节 黄斑致密球旁小球介导的肾小管流量 仪器。绿色贸易壁垒与转化生长因子共同构成一个“转化生长因子系统”， 定义了SNGFR和VLP的双向相互依赖关系。然而，这些 关系不是固定的，必须允许改变才能 保持生理灵活性。SNGFR和SNGFR关系的变化 VLP或转化生长因子适应随着时间的推移而发生，以响应强加的、持续的 SNGFR的提升和Proxima吸收的减少，就像我们所做的 在服用苯妥拉胺期间显示，苯甲酰胺是一种 近端肾小管重吸收。在线视频流量测速仪 技术允许重复评估转化生长因子补偿和 监测中对转化生长因子适应模式的定量评估 致密黄斑通过远端小管离子电导传入转化生长因子信号 电极和肾小球血流动力学评价效应器 转化生长因子的作用机制。对转化生长因子适应至关重要的因素是a) Henle-粗升肢(TAL)重吸收环的变化 容量，b)致密黄斑信号传输和c)适应 肾小球血流动力学效应机制。具体目标#1--转化生长因子适应 由于1)适应性，近端重吸收持续减少 Henle/TAL重吸收环的增加和2)修改 一氧化氮合酶(NOS)，特别是神经元型一氧化氮合酶(BNOS)。特定的 目标2-转化生长因子可能起到限制与环路相关的能量消耗的作用 Henle重吸收，以及局部PO2和单加氧酶系统将 用PO2微电极进行评估，O2释放的变化和 酶抑制剂。肾小管远端管段的作用 致密黄斑到转化生长因子信号也将被评估。具体目标#3- 我们认为肾毒性急性肾功能衰竭(硝酸铀酰)代表 转化生长因子适应性受损导致持续性转化生长因子1例 激活。他可能是由于不能增加Henle环所致 重吸收、改变一氧化氮合酶活性或改变转化生长因子信号的效应器 机械装置。阐明转化生长因子适应的正常机制是一个 加深对肾脏病理生理认识的前提 可能表现出转化生长因子适应受损的情况。

Normal kidney function requires the close coordination of glomerular filtration and tubular reabsorption in order to prevent major swings in volume status. This coordination is largely mediated by the processes of glomerular tubular balance (GTB) which is the flow dependence of tubular reabsorption, and tubuloglomerular feedback (TGF), which is the negative feedback regulation of nephron filtration rate (SNGFR) by late proximal tubular flow rate (vLP) mediated by the macula-densa-juxtaglomerular apparatus. GTB and TGF combine to constitute a "TGF system" which defines a two way interdependence of SNGFR and VLP. However, these relations are not fixed and must be allowed to change in order to maintain physiologic flexibility. Changes in the relation of SNGFR and VLP, or TGF adaptation occur over time in response to imposed, sustained elevations in SNGFR and reductions in proxima absorption, as we have demonstrated during the administration of benzolamide, an inhibitor of proximal tubular reabsorption. Online videometric flow velocitometric techniques permit repetitive assessments of TGF compensation and quantitative assessment of the mode of TGF adaptation while monitoring macula densa afferent TGF signals via distal tubule ionic conductivity electrodes and glomerular hemodynamic evaluations of the effector mechanisms of TGF. The elements critical to TGF adaptation are a) changes in loop of Henle - thick ascending limb (TAL) reabsorptive capacity, b) macula densa signal transmission and c) adaptations of the glomerular hemodynamic effector mechanism. Specific Aim #1- TGF adapts to sustained reductions in proximal reabsorption due to 1) adaptive increases in Loop of Henle/TAL reabsorption and 2) modifications in nitric oxide synthase (NOS), specifically neuronal NOS (bNOS). Specific Aim #2- TGF may function to limit energy consumption linked to loop of Henle reabsorption, and local pO2 and monooxygenase enzyme systems will be assessed with pO2 micro- electrodes, variations in 02 delivery and enzyme inhibitors. The contributions of tubular segments distal to the macula densa to TGF signalling will also be assessed. Specific Aim #3 - We propose nephrotoxic acute renal failure (uranyl nitrate) represents an example of impaired TGF adaptation, resulting in persistent TGF activation. his may result from inability to increase loop of Henle reabsorption, modify NOS activity or alter TGF signals t he effector mechanisms. Elucidation of the normal mechanisms of TGF adaptation is a prerequisite for the further understanding of renal pathophysiologic conditions which may exhibit impaired TGF adaptation.