Ablation of the Cl-/HCO3- Exchanger Pendrin Enhances Hydrochlorothiazide-Induced Diuresis.
Ablation of the Cl-/HCO3- Exchanger Pendrin Enhances Hydrochlorothiazide-Induced Diuresis.
复制标题
Cl-/HCO3- 交换剂 Pendrin 的消融增强氢氯噻嗪诱导的利尿。
DOI：
10.1159/000479296
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发表时间：
2017
影响因子：
2.8
通讯作者：
Soleimani,Manoocher
中科院分区：
文献类型：
--
作者：
Alshahrani,Saeed;Soleimani,Manoocher
背景/目的Cl-/HCO 3-交换蛋白pendrin和噻嗪敏感性Na-Cl协同转运蛋白NCC在肾脏远端肾单位表达并介导盐的吸收。我们假设，删除pendrin叶NCC作为主要的盐吸收转运蛋白在远端肾单位，因此提高盐排泄氢氯噻嗪（HCTZ）。MethodsMetabolic笼研究进行野生型，pendrin KO和NCC KO小鼠在基线和HCTZ治疗后。在平行的研究中，全身血压测定与HCTZ治疗的小鼠与尾袖method.ResultsUrine输出量，盐排泄量和水的摄入量在基线条件下，在所有组中是可比的。仅在pendrin KO小鼠中对HCTZ有反应时，尿量和水摄入量显著增加，但在WT或NCC KO小鼠中没有。在HCTZ处理的pendrin KO小鼠中，钠和氯排泄增加，但在WT或NCC KO小鼠中保持不变。用HCTZ处理的Pendrin KO小鼠出现血容量减少，如通过增加的肾素mRNA和蛋白质表达所确定的。HCTZ处理的WT小鼠中ENaC和pendrin的表达增加。HCTZ治疗没有显着修改血压在任何实验group.ConclusionThe消融的Cl-/HCO 3-交换Pendrin增强的幅度盐浪费HCTZ。
Background/AimsThe Cl-/HCO 3-exchanger pendrin and the thiazide-sensitive Na-Cl cotransporter NCC are expressed in the kidney distal nephron and mediate salt absorption. We hypothesized that deletion of pendrin leaves NCC as the major salt absorbing transporter in the distal nephron and therefore enhances salt excretion by hydrochlorothiazide (HCTZ).MethodsMetabolic cage studies were performed in wild type, pendrin KO and NCC KO mice at baseline and following HCTZ treatment. In parallel studies, systemic blood pressure was measured in mice treated with HCTZ with the tail cuff method.ResultsUrine output, salt excretion and water intake were comparable in all groups under baseline condition. Urine output and water intake increased significantly only in pendrin KO mice in response to HCTZ, but not in WT or NCC KO mice. Sodium and chloride excretion increased in HCTZ-treated pendrin KO mice, but they remained unchanged in WT or NCC KO mice. Pendrin KO mice treated with HCTZ developed volume depletion, as determined by increased expression of renin mRNA and protein. The expression of ENaC and pendrin increased in HCTZ-treated WT mice. HCTZ treatment did not significantly modify blood pressure in any of the experimental group.ConclusionThe ablation of the Cl-/HCO 3-exchanger Pendrin enhances the magnitude of salt wasting by HCTZ.