Yip K P, Tse C M, McDonough A A, Marsh D J
Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Providence, Rhode Island 02912, USA.
Am J Physiol. 1998 Oct;275(4):F565-75. doi: 10.1152/ajprenal.1998.275.4.F565.
Redistribution of apical Na+/H+ exchangers (NHE) in the proximal tubules as a plausible mechanism of pressure natriuresis was investigated with confocal immunofluorescence microscopy in Sprague-Dawley rats (SD), spontaneously hypertensive rats (SHR), and two-kidney, one-clip Goldblatt hypertensive rats (GH). NHE isoform NHE3 was localized in the brush border of proximal tubules in SD. Twenty minutes of induced acute hypertension (20-40 mmHg) resulted in a pronounced redistribution of isoform NHE3 from the brush border into the base of microvilli, where clathrin-coated pits were localized. Prehypertensive young SHR (5 wk old, mean blood pressure 105 +/- 3 mmHg, n = 11) produced similar findings. However, NHE3 was found to concentrate in the base of microvilli in adult SHR (12 wk old, mean blood pressure 134 +/- 6 mmHg, n = 12) and nonclipped kidneys of GH (mean blood pressure 131 +/- 6 mmHg, n = 6). In clipped kidneys of GH, which were not exposed to the hypertension because of the arterial clips, NHE3 was localized on the brush border as in normal SD. No further redistribution of NHE3 was detected in adult SHR or GH when acute hypertension was induced. Since both acute and chronic increase of arterial pressure can provoke the redistribution of apical NHE in proximal tubules, the pressure-induced NHE redistribution could be a physiological response and an integral part of pressure natriuresis.
运用共聚焦免疫荧光显微镜技术，在斯普拉格-道利大鼠（SD）、自发性高血压大鼠（SHR）以及两肾一夹型戈德布拉特高血压大鼠（GH）中，研究近端小管顶端钠氢交换体（NHE）的重新分布，以此作为压力性利钠的一种可能机制。NHE亚型NHE3定位于SD大鼠近端小管的刷状缘。诱导急性高血压20分钟（20 - 40 mmHg）导致NHE3亚型从刷状缘显著重新分布至微绒毛基部，而网格蛋白包被小窝位于此处。高血压前期的年轻SHR（5周龄，平均血压105±3 mmHg，n = 11）产生了类似的结果。然而，在成年SHR（12周龄，平均血压134±6 mmHg，n = 12）和GH大鼠的未夹闭肾脏（平均血压131±6 mmHg，n = 6）中，发现NHE3集中在微绒毛基部。在GH大鼠的夹闭肾脏中，由于动脉夹的存在未暴露于高血压状态，NHE3如在正常SD大鼠中一样定位于刷状缘。当诱导急性高血压时，在成年SHR或GH大鼠中未检测到NHE3的进一步重新分布。由于动脉压的急性和慢性升高均可引发近端小管顶端NHE的重新分布，压力诱导的NHE重新分布可能是一种生理反应，并且是压力性利钠的一个组成部分。
