NaCl restriction upregulates renal Slc26a4 through subcellular redistribution: role in Cl- conservation.
NaCl restriction upregulates renal Slc26a4 through subcellular redistribution: role in Cl- conservation.
复制标题
氯化钠限制通过亚细胞重新分布上调肾脏 Slc26a4：在 Cl- 保存中的作用。
DOI：
10.1161/01.hyp.0000145863.96091.89
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发表时间：
2004
期刊：
影响因子：
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通讯作者：
Verlander,JillW
中科院分区：
文献类型：
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作者：
Wall,SusanM;Kim,YoungHee;Stanley,Lorraine;Glapion,DawnM;Everett,LorraineA;Green,EricD;Verlander,JillW
Slc26a4 （Pds, pendrin）是一种阴离子转运蛋白，表达于肾远端B型和非a、非B插层细胞的根尖区。它被醛固酮类似物上调，在矿化皮质激素诱导的高血压的发展中是至关重要的。因此，在适当增加醛固酮的NaCl限制处理模式下，我们探讨了slc26a4的表达及其在血压和体液电解质稳态中的作用。采用超微结构免疫定位、平衡研究和体外灌注皮质集管（CCDs）。在适度的生理NaCl限制下，B型插层细胞顶端质膜上slc26a4的表达增加了2- 3倍。由于eslc26a4转运Cl−，我们测试了在NaCl限制期间，slc26a4（+/+）和slc26a4（−/−）小鼠的NaCl平衡是否不同。在slc26a4（+/+）小鼠的ccd中观察到Cl -吸收，而在slc26a4（- /−）小鼠的ccd中没有。适度NaCl限制后，相对于slc26a4（+/+）小鼠，slc26a4的尿量和Cl -排泄量（−/−）增加。此外，Slc26a4（−/−）小鼠有相对血管体积减少的证据，因为它们的动脉pH值、红细胞压积和血液尿素氮比野生型小鼠高。在适度NaCl限制下，slc26a4（+/+）和slc26a4（−/−）小鼠的血压相似。然而，在严格限制NaCl摄入量的情况下，Slc26a4（−/−）小鼠相对于野生型小鼠具有低血压。我们得出结论，slc26a4在NaCl限制下上调，并且在维持酸碱平衡和在NaCl限制下肾脏中Cl -和水的保存中起关键作用。
Slc26a4 (Pds, pendrin) is an anion transporter expressed in the apical region of type B and non-A, non-B intercalated cells of the distal nephron. It is upregulated by aldosterone analogues and is critical in the development of mineralocorticoid-induced hypertension. Thus,Slc26a4expression and its role in blood pressure and fluid and electrolyte homeostasis was explored during NaCl restriction, a treatment model in which aldosterone is appropriately increased. Ultrastructural immunolocalization, balance studies, and cortical collecting ducts (CCDs) perfused in vitro were used. With moderate physiological NaCl restriction,Slc26a4expression in the apical plasma membrane increased 2- to 3-fold in type B intercalated cells. BecauseSlc26a4transports Cl−, we tested whether NaCl balance differs inSlc26a4(+/+)andSlc26a4(−/−)mice during NaCl restriction. Cl−absorption was observed in CCDs fromSlc26a4(+/+)but not fromSlc26a4(−/−)mice. After moderate NaCl restriction, urinary volume and Cl−excretion were increased inSlc26a4(−/−)relative toSlc26a4(+/+)mice. Moreover,Slc26a4(−/−)mice had evidence of relative vascular volume depletion because they had a higher arterial pH, hematocrit, and blood urea nitrogen than wild-type mice. With moderate NaCl restriction, blood pressure was similar inSlc26a4(+/+)andSlc26a4(−/−)mice. However, on a severely restricted intake of NaCl,Slc26a4(−/−)mice were hypotensive relative to wild-type mice. We conclude thatSlc26a4is upregulated with NaCl restriction and is critical in the maintenance of acid-base balance and in the renal conservation of Cl−and water during NaCl restriction.