Peti-Peterdi J, Bell P D
Department of Medicine, University of Alabama, Birmingham, USA.
Kidney Int. 1998 Dec;54(6):2021-8. doi: 10.1046/j.1523-1755.1998.00200.x.
Angiotensin II (Ang II) is a positive modulator of tubuloglomerular feedback (TGF). At the present time, the site(s) at which Ang II interacts with the signal transmission process remains unknown. In certain renal epithelia, Ang II is known to stimulate apical Na:H exchange. Since macula densa cells possess an apical Na:H exchanger and Ang II subtype I receptors (AT1-receptors), we tested the possibility that Ang II might stimulate exchanger activity in these cells.
Using the isolated perfused thick ascending limb with attached glomerulus preparation dissected from rabbit kidney, macula densa intracellular pH (pHi) was measured with fluorescence microscopy using BCECF.
Control pHi, during perfusion with 25 mM NaCl and 150 mM NaCl in the bath, averaged 7.22 +/- 0.02 (N = 24). Increasing luminal [NaCl] to 150 mM elevated pHi by 0.54 +/- 0.04 (N = 7, P < 0.01). Ang II (10(-9) M), added to the bath in the same paired experiments, significantly elevated baseline pHi by 0.17 +/- 0.04, increased the magnitude of change in pHi (delta = 0.71 +/- 0.05) and initial rate of alkalinization (by 69%) to increased luminal [NaCl]. Ang II produced similar effects when added exclusively to the luminal perfusate. In addition, low-dose Ang II (10(-9) M) stimulated while high-dose Ang II (10(-6) M) inhibited Na-dependent pH-recovery from an acid load. AT1 blockade prevented the stimulatory but not the inhibitory effects of Ang II.
Through the AT1, Ang II may influence macula densa Na transport and regulate cell alkalinization via the apical Na:H exchanger. Thus, Ang II may modulate the TGF signal transmission process, at least in part, through a direct effect on macula densa cell function.
血管紧张素II（Ang II）是管球反馈（TGF）的正向调节因子。目前，Ang II与信号传导过程相互作用的位点尚不清楚。在某些肾上皮细胞中，已知Ang II可刺激顶端Na⁺/H⁺交换。由于致密斑细胞具有顶端Na⁺/H⁺交换体和Ang II 1型受体（AT1受体），我们测试了Ang II可能刺激这些细胞中交换体活性的可能性。
使用从兔肾分离的带有附着肾小球的灌注厚升支制备物，采用荧光显微镜利用BCECF测量致密斑细胞内pH值（pHi）。
在浴液中灌注25 mM NaCl和150 mM NaCl期间，对照pHi平均为7.22±0.02（N = 24）。将管腔[NaCl]增加到150 mM使pHi升高0.54±0.04（N = 7，P < 0.01）。在相同的配对实验中，添加到浴液中的Ang II（10⁻⁹ M）使基线pHi显著升高0.17±0.04，增加了pHi的变化幅度（δ = 0.71±0.05）以及管腔[NaCl]增加时的初始碱化速率（增加69%）。当仅添加到管腔灌注液中时，Ang II产生类似的效果。此外，低剂量Ang II（10⁻⁹ M）具有刺激作用，而高剂量Ang II（10⁻⁶ M）抑制酸负荷后Na⁺依赖的pH恢复。AT1阻断可防止Ang II的刺激作用，但不能防止其抑制作用。
通过AT1，Ang II可能影响致密斑Na⁺转运，并通过顶端Na⁺/H⁺交换体调节细胞碱化。因此，Ang II可能至少部分地通过对致密斑细胞功能的直接作用来调节TGF信号传导过程。
