Theoretical assessment of renal autoregulatory mechanisms.
Theoretical assessment of renal autoregulatory mechanisms.
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肾脏自动调节机制的理论评估。
DOI：
10.1152/ajprenal.00649.2013
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Layton,AnitaT
中科院分区：
文献类型：
--
作者：
Sgouralis,Ioannis;Layton,AnitaT
肾血流动力学的数学模型被用来评估肾小管肾小球反馈（TGF）机制和肌源性反应的肾小球滤过率调节在大鼠肾脏的个人贡献。该模型代表了一个传入小动脉段，肾小球滤过，和一个短的亨利环。传入小动脉模型表现出肌源性反应，其被流体静压变化激活以诱导膜电位和血管肌张力的变化。小管模型预测了小管液体和Cl−的运输。致密斑Cl−浓度被认为是TGF的信号，TGF的作用是收缩或扩张传入小动脉。通过这种配置，模型传入小动脉在灌注压的生理范围（80-180 mmHg）内保持稳定的肾小球滤过率。TGF对整体自动调节的贡献仅在灌注压值的窄带（80-110 mmHg）内是显著的。斜坡状灌注压力扰动的模型模拟与Flemming等人的发现（Flemming B，Arenz N，Seeliger E，Wronski T，Steer K，Closson PB.J Am Soc Nephrol 12：2253-2262，2001）很好地一致，这表明血管传导性的变化对压力速度显著敏感。这种不对称的反应归因于生肌机制的速率依赖性动力学。此外，模拟糖尿病中的肾自动调节预测，由于传入小动脉平滑肌细胞的电压门控Ca 2+通道受损，单肾单位肾小球滤过率保持稳定的灌注压范围降低了约70%，TGF增益降低了近40%，与实验结果一致。
A mathematical model of renal hemodynamics was used to assess the individual contributions of the tubuloglomerular feedback (TGF) mechanism and the myogenic response to glomerular filtration rate regulation in the rat kidney. The model represents an afferent arteriole segment, glomerular filtration, and a short loop of Henle. The afferent arteriole model exhibits myogenic response, which is activated by hydrostatic pressure variations to induce changes in membrane potential and vascular muscle tone. The tubule model predicts tubular fluid and Cl−transport. Macula densa Cl−concentration is sensed as the signal for TGF, which acts to constrict or dilate the afferent arteriole. With this configuration, the model afferent arteriole maintains stable glomerular filtration rate within a physiologic range of perfusion pressure (80–180 mmHg). The contribution of TGF to overall autoregulation is significant only within a narrow band of perfusion pressure values (80–110 mmHg). Model simulations of ramp-like perfusion pressure perturbations agree well with findings by Flemming et al. (Flemming B, Arenz N, Seeliger E, Wronski T, Steer K, Persson PB.J Am Soc Nephrol12: 2253–2262, 2001), which indicate that changes in vascular conductance are markedly sensitive to pressure velocity. That asymmetric response is attributed to the rate-dependent kinetics of the myogenic mechanism. Moreover, simulations of renal autoregulation in diabetes mellitus predict that, due to the impairment of the voltage-gated Ca2+channels of the afferent arteriole smooth muscle cells, the perfusion pressure range in which single-nephron glomerular filtration rate remains stable is reduced by ∼70% and that TGF gain is reduced by nearly 40%, consistent with experimental findings.