INSTANTANEOUS AND STEADY-STATE GAINS IN THE TUBULOGLOMERULAR FEEDBACK-SYSTEM
INSTANTANEOUS AND STEADY-STATE GAINS IN THE TUBULOGLOMERULAR FEEDBACK-SYSTEM
复制标题
DOI：
10.1152/ajprenal.1995.268.1.f163
复制
发表时间：
1995-01-01
期刊：
影响因子：
--
通讯作者：
MOORE, LC
中科院分区：
文献类型：
--
作者：
LAYTON, HE;PITMAN, EB;MOORE, LC
进入哺乳动物肾脏的每个肾单位的水和溶质的负荷由肾小管肾小球反馈（TGF）机制（负反馈回路）调节。大鼠实验表明，该反馈系统的关键变量可能表现出TGF介导的振荡。数学建模研究表明，开环反馈增益是决定是否会出现振荡的关键参数。然而，已经使用了这种增益的两种不同的公式。第一个是稳态增益，这是一个容易测量的量，对应于上行肢体流速持续增加后单肾单位肾小球滤过率（SNGFR）的稳态降低。第二个是瞬时增益，这是一个从理论考虑中产生的变量，对应于由上升支流柱的瞬时移位引起的SNGFR的最大降低，假设SNGFR响应也是瞬时的。在这里，我们展示了一个分析参数如何上升的肢体的稳态和瞬时开环反馈回路增益的相关。在没有溶质回漏到上升分支的情况下，两种增益公式是等效的;然而，在存在溶质回漏的情况下，瞬时增益的幅度大于稳态增益。用大鼠的典型生理参数，用我们以前设计的模型计算表明，增益相差5- 10%。因此，稳态增益的实验测量可以提供有用的下限估计的反馈系统的瞬时增益在正常大鼠。然而，收益可能会分歧显着的病理生理状态，其中上升肢体运输受到异常高的NaCl渗透性。
The load of water and solute entering each nephron of the mammalian kidney is regulated by the tubuloglomerular feedback (TGF) mechanism, a negative feedback loop. Experiments in rats have shown that key Variables of this feedback system may exhibit TGF-mediated oscillations. Mathematical modeling studies have shown that the open-feedback-loop gain is a crucial parameter for determining whether oscillations will emerge. However, two different formulations of this gain have been used. The first is the steady-state gain, a readily measurable quantity corresponding to the steady-state reduction in single-nephron glomerular filtration rate (SNGFR) subsequent to a sustained increase in ascending limb flow rate. The second is an instantaneous gain, a variable arising from theoretical considerations corresponding to the maximum reduction in SNGFR resulting from an instantaneous shift of the ascending limb flow column, with the assumption that the SNGFR response is also instantaneous. Here we show by an analytic argument how the steady-state and instantaneous open-feedback-loop gains for the ascending limb are related. In the case of no solute backleak into the ascending limb, the two formulations of gain are equivalent; however, in the presence of solute backleak, the instantaneous gain is larger in magnitude than the steady-state gain. With typical physiological parameters for the rat, calculations with a model previously devised by us show that the gains differ by 5-10%. Hence, experimental measurements of the steady-state gain may provide useful lower-bound estimates of the instantaneous gain of the feedback system in the normal rat. However, the gains may diverge significantly in pathophysiological states where ascending limb transport is compromised by abnormally high NaCl permeability.