Laboratory of Receptor and Signal Transduction, Department of Pharmacology and Toxicology; Division of Nephrology, Internal Medicine; Cardiovascular and Renal Research Center; The University of Mississippi Medical Center , Jackson, Mississippi.
Physiol Genomics. 2019 Apr 1;51(4):97-108. doi: 10.1152/physiolgenomics.00122.2018. Epub 2019 Mar 8.
The sodium (Na)/hydrogen (H) exchanger 3 (NHE3) and sodium-potassium adenosine triphosphatase (Na/K-ATPase) are two of the most important Na transporters in the proximal tubules of the kidney. On the apical membrane side, NHE3 primarily mediates the entry of Na into and the exit of H from the proximal tubules, directly and indirectly being responsible for reabsorbing ~50% of filtered Na in the proximal tubules of the kidney. On the basolateral membrane side, Na/K-ATPase serves as a powerful engine driving Na out of, while pumping K into the proximal tubules against their concentration gradients. While the roles of NHE3 and Na/K-ATPase in proximal tubular Na transport under in vitro conditions are well recognized, their respective contributions to the basal blood pressure regulation and angiotensin II (ANG II)-induced hypertension remain poorly understood. Recently, we have been fortunate to be able to use genetically modified mouse models with global, kidney- or proximal tubule-specific deletion of NHE3 to directly determine the cause and effect relationship between NHE3, basal blood pressure homeostasis, and ANG II-induced hypertension at the whole body, kidney and/or proximal tubule levels. The purpose of this article is to review the genetic and genomic evidence for an important role of NHE3 with a focus in the regulation of basal blood pressure and ANG II-induced hypertension, as we learned from studies using global, kidney- or proximal tubule-specific NHE3 knockout mice. We hypothesize that NHE3 in the proximal tubules is necessary for maintaining basal blood pressure homeostasis and the development of ANG II-induced hypertension.
钠/氢交换器 3（NHE3）和钠-钾三磷酸腺苷酶（Na/K-ATPase）是肾脏近曲小管中最重要的两种钠转运体。在顶端膜侧，NHE3 主要介导 Na 的进入和 H 的排出，直接和间接负责重吸收肾脏近曲小管中滤过的 Na 的约 50%。在基底外侧膜侧，Na/K-ATPase 作为一种强大的引擎，将 Na 泵出，同时将 K 泵入近曲小管，逆其浓度梯度。虽然在体外条件下 NHE3 和 Na/K-ATPase 在近端管状 Na 转运中的作用已得到充分认识，但它们各自对基础血压调节和血管紧张素 II（ANG II）诱导的高血压的贡献仍知之甚少。最近，我们有幸能够使用具有全局、肾脏或近曲小管特异性 NHE3 缺失的基因修饰小鼠模型，直接确定 NHE3、基础血压稳态和 ANG II 诱导的高血压之间的因果关系，在全身、肾脏和/或近曲小管水平。本文的目的是综述 NHE3 在调节基础血压和 ANG II 诱导的高血压方面的遗传和基因组证据，这是我们从使用全局、肾脏或近曲小管特异性 NHE3 敲除小鼠的研究中了解到的。我们假设近曲小管中的 NHE3 对于维持基础血压稳态和 ANG II 诱导的高血压的发展是必要的。
