Bell P D, Peti-Peterdi J
Nephrology Research and Training Center, Department of Medicine, University of Alabama at Birmingham, 35294, USA.
J Am Soc Nephrol. 1999 Jan;10 Suppl 11:S225-9.
Angiotensin II (AngII) enhances tubuloglomerular feedback responses and is considered to be a specific modulator of feedback activity. The sites at which AngII interacts with the signal transmission process remain unknown. In certain renal epithelia, AngII stimulates Na/H exchange activities. Evidence for the regulation of macula densa apical Na/H exchange by AngII was recently reported. Because macula densa cells also express a basolateral Na/H exchanger, the possibility that AngII stimulates this exchanger activity was investigated. In preparations of isolated perfused thick ascending limb with attached glomerulus dissected from rabbit kidney, the intracellular pH (pHi) of macula densa cells was measured with fluorescence microscopy using 2',7'-bis(2-carboxyethyl)-5-(and -6)carboxyfluorescein. Perfusion and bathing solutions were iso-osmotic Cl-free Ringer's solutions modified using N-methyl-D-glucamine and cyclamate as the Na and Cl substitutes, respectively. Control pHi, during perfusion with 0 mM Na and 150 mM Na in the bath, averaged 7.21+/-0.07 (n=10). Removal of Na from the bath (i.e., basolateral solution) decreased pHi by 0.39+/-0.06 units (n=5, P < 0.01). Addition of 10(-9) M AngII to the bath resulted in a significant increase in the Na-dependent acid load. This increase in Na-dependent cell acidification was completely blocked by coadministration of the AngII type 1 (AT1) receptor blocker candesartan (10(-8) M). In addition, AngII increased the rate of pHi recovery from the acid load induced by readdition of bath Na. This stimulatory effect of AngII was also completely reversed by coadministration of the AT1 receptor blocker candesartan. These results indicate that AngII stimulates macula densa basolateral Na/H exchange via AT1 receptors and therefore may affect tubuloglomerular feedback signal transmission, at least in part, through direct effects on macula densa transport processes.
血管紧张素II（AngII）增强肾小管-肾小球反馈反应，被认为是反馈活动的一种特异性调节因子。AngII与信号传递过程相互作用的位点尚不清楚。在某些肾上皮细胞中，AngII刺激钠/氢交换活动。最近有报道称有证据表明AngII对致密斑顶端钠/氢交换有调节作用。由于致密斑细胞也表达一种基底外侧钠/氢交换体，因此研究了AngII刺激这种交换体活性的可能性。在从兔肾分离的带有附着肾小球的灌注厚升支制备物中，使用2',7'-双（2-羧乙基）-5-（和-6）羧基荧光素通过荧光显微镜测量致密斑细胞的细胞内pH（pHi）。灌注液和浴液分别是用N-甲基-D-葡糖胺和环己基氨基磺酸盐作为钠和氯替代物改良的等渗无氯林格氏液。在浴中用0 mM钠灌注且浴中为150 mM钠时，对照pHi平均为7.21±0.07（n = 10）。从浴中去除钠（即基底外侧溶液）使pHi降低0.39±0.06个单位（n = 5，P < 0.01）。向浴中添加10^(-9) M AngII导致钠依赖性酸负荷显著增加。这种钠依赖性细胞酸化的增加被同时给予血管紧张素II 1型（AT1）受体阻滞剂坎地沙坦（10^(-8) M）完全阻断。此外，AngII增加了因重新添加浴中钠而诱导的酸负荷后pHi的恢复速率。AngII的这种刺激作用也被同时给予AT1受体阻滞剂坎地沙坦完全逆转。这些结果表明，AngII通过AT1受体刺激致密斑基底外侧钠/氢交换，因此可能至少部分地通过对致密斑转运过程的直接作用来影响肾小管-肾小球反馈信号传递。
