A DYNAMIC-MODEL OF THE TUBULOGLOMERULAR FEEDBACK MECHANISM
A DYNAMIC-MODEL OF THE TUBULOGLOMERULAR FEEDBACK MECHANISM
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DOI：
10.1152/ajprenal.1990.258.5.f1448
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发表时间：
1990-05-01
影响因子：
--
通讯作者：
MARSH, DJ
中科院分区：
文献类型：
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作者：
HOLSTEINRATHLOU, NH;MARSH, DJ
我们报道了氟烷麻醉的 Sprague-Dawley 大鼠中近端肾小管压力和流量以及远端肾小管压力和氯化物浓度的振荡。这些变量在每只动物中以相同的频率（大约 35 mHz）振荡，但彼此异相。我们认为振荡出现在肾小球反馈（TGF）系统内。作为对这一假设的检验，我们现在开发了一个动态模型，以确定它是否可以使用一组实际参数来模拟测量的频率和相位关系。该模型包括基于纳维-斯托克斯方程简化版本的管内压力和流量的详细表示。致密斑处的 NaCl 浓度被用作 TGF 机制的信号。通过基于质量守恒的偏微分方程对管状 NaCl 浓度进行建模。对于一组实际的参数值，该模型准确地预测了振荡，其频率和振荡变量之间的相位关系与实验发现的相同。此外，管状 NaCl 处理显着影响 TGF 系统的动态特性。因此，该模型预测了 NaCl 浓度相对于致密斑处的流动振荡的显着相移。结果与振荡由 TGF 机制引起的假设一致。结果进一步支持这样的观点，即肾小管引起的延迟和阻尼是肾自动调节的有限高频响应的原因。
We have reported oscillations in proximal tubular pressure and flow and in distal tubular pressure and chloride concentration in halothane-anesthetized Sprague-Dawley rats. These variables oscillated at the same frequency in each animal, approximately 35 mHz, but were out of phase with each other. We suggested that the oscillation arises within the tubuloglomerular feedback (TGF) system. As a test of this hypothesis, we have now developed a dynamic model to determine whether it can simulate the measured frequency and phase relationships with a realistic set of parameters. The model includes a detailed representation of pressure and flow in the tubules based on a reduced version of the Navier-Stokes equations. The NaCl concentration at the macula densa was used as the signal to the TGF mechanism. The tubular NaCl concentration was modeled by a partial differential equation based on conservation of mass. For a realistic set of parameter values the model accurately predicted oscillations with the same frequency and phase relationships among the oscillating variables as was found experimentally. Moreover, tubular NaCl handling significantly influenced the dynamic properties of the TGF system. Thus the model predicted a substantial phase shift of the NaCl concentration relative to the flow oscillation at the macula densa. The results are consistent with the hypothesis that the oscillations are caused by the TGF mechanism. The results further support the notion that the delays and damping caused by the tubule are responsible for the limited high-frequency response of renal autoregulation.