AUTOREGULATION OF GLOMERULAR FILTRATION RATE
AUTOREGULATION OF GLOMERULAR FILTRATION RATE
批准号:
6083834
负责人:
ROLAND C BLANTZ
金额:
$1.61万
依托单位国家:
美国
项目类别:
财政年份:
1999
资助国家:
美国
项目状态:
已结题
起止时间:
1999-07-01 至 1999-09-29
中文摘要
正常的肾功能需要肾小球的密切协调,
过滤和肾小管重吸收,以防止
卷状态。这种协调在很大程度上是由以下过程介导的:
肾小球肾小管平衡(GTB)是肾小管的流量依赖性,
重吸收和肾小管肾小球反馈(TGF),这是负面的
肾单位滤过率(SNGFR)的反馈调节
肾小管流速(vLP)由黄斑-致密-肾小球介导
设备. GTB和TGF联合收割机组成“TGF系统”,
定义了SNGFR和VLP的双向相互依赖性。但这些
关系不是固定的,必须允许改变,
保持生理灵活性。SNGFR与
VLP或TGF适应随着时间的推移发生,以响应强加的,持续的
SNGFR升高和近端吸收减少,正如我们所做的那样,
在给予苯甲酰胺(一种
近端肾小管重吸收。 在线视频流速仪
技术允许重复评估TGF补偿,
定量评估TGF适应模式,同时监测
致密斑通过远端小管离子传导传入TGF信号
电极和效应器的肾小球血流动力学评价
TGF的机制。TGF适应的关键因素是a)
Henle袢的变化-粗升支(TAL)重吸收
容量,B)致密斑信号传输和c)
肾小球血流动力学效应机制。具体目标#1- TGF适应
持续减少近端重吸收,由于1)适应性
Henle环/TAL重吸收增加和2)
一氧化氮合酶(NOS),特别是神经元NOS(bNOS)。具体
目标#2- TGF可以起到限制与循环相关的能量消耗的作用。
Henle重吸收,局部pO 2和单加氧酶系统将
用pO 2微电极、O2输送的变化和
酶抑制剂远端管段的贡献
还将评估致密斑对TGF信号传导的影响。具体目标#3 -
我们提出肾毒性急性肾衰竭(硝酸铀酰)代表
一个TGF适应受损的例子,导致持续的TGF
activation.这可能是由于不能增加亨利环
重吸收,改变NOS活性或改变TGF信号
机制等阐明TGF适应的正常机制是一个重要的研究课题。
进一步了解肾脏病理生理的前提
可能表现出受损的TGF适应的病症。
英文摘要
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.
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Autoregulation of Glomerular Filtration Rate
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批准号:7913926
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资助金额:$10.6万
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财政年份:2009
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资助金额:$0.0万
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资助金额:$0.0万
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AUTOREGULATION OF GLOMERULAR FILTRATION RATE
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批准号:8526490
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资助金额:$24.86万
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财政年份:1996
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依托单位:
海外基金