Impaired urine concentration and absence of tissue ACE: involvement of medullary transport proteins.
Impaired urine concentration and absence of tissue ACE: involvement of medullary transport proteins.
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尿液浓度受损和组织 ACE 缺失：髓质转运蛋白参与。
DOI：
10.1152/ajprenal.00326.2001
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Sands,JeffM
中科院分区：
文献类型：
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作者：
Klein,JanetD;LeQuach,D;Cole,JustinM;Disher,Kevin;Mongiu,AnneK;Wang,Xiaodan;Bernstein,KennethE;Sands,JeffM
ACE.2小鼠缺乏所有组织血管紧张素转换酶（ACE），但血浆ACE活性为正常水平的33%。它们表现出尿浓缩缺陷和高钾血症，存在于缺乏所有ACE的小鼠中，但与完全敲除ACE的小鼠相反，ACE.2小鼠的髓质组织学和肌酐清除率正常。为了探讨ACE.2小鼠的尿浓缩缺陷，采用Western blot分析肾髓质转运蛋白。髓质内UT-A1、ClC-K1和水通道蛋白1 （AQP1）水平分别显著降低至野生型小鼠的28±5%、6±6%和39±5%，而AQP2和UT-B水平不变。外髓内Na+-K+-2Cl−共转运体（NKCC2/BSC1）和AQP1分别显著降低至56±11%和29±6%，而Na+-K+-ATPase、UT-A2、UT-B和AQP2不变，肾外髓钾通道显著增加至野生型小鼠的711±187%。这些转运蛋白的异常表达在回交C57BL/6或瑞士背景的ACE.2小鼠中是相似的，并且不能通过ANG II输注来挽救。我们得出结论，ACE.2小鼠的尿浓缩缺陷与部分或全部这些关键尿素、盐和水转运蛋白的下调有关，并可能由其导致。
ACE.2 mice lack all tissue angiotensin-converting enzyme (ACE) but have 33% of normal plasma ACE activity. They exhibit the urine-concentrating defect and hyperkalemia present in mice that lack all ACE, but in contrast to the complete knockout, ACE.2 mice have normal medullary histology and creatinine clearance. To explore the urine-concentrating defect in ACE.2 mice, renal medullary transport proteins were analyzed using Western blot analysis. In the inner medulla, UT-A1, ClC-K1, and aquaporin-1 (AQP1) were significantly reduced to 28 ± 5, 6 ± 6, and 39 ± 5% of the level in wild-type mice, respectively, whereas AQP2 and UT-B were unchanged. In the outer medulla, Na+-K+-2Cl−cotransporter (NKCC2/BSC1) and AQP1 were significantly reduced to 56 ± 11 and 29 ± 6%, respectively, whereas Na+-K+-ATPase, UT-A2, UT-B, and AQP2 were unchanged, and renal outer medullary potassium channel was significantly increased to 711 ± 187% of the level in wild-type mice. The abnormal expression of these transporters was similar in ACE.2 mice backcrossed onto a C57BL/6 or a Swiss background and was not rescued by ANG II infusion. We conclude that the urine-concentrating defect in ACE.2 mice is associated with, and may result from, downregulation of some or all of these key urea, salt, and water transport proteins.