Genetic and genomic evidence for an important role of the Na⁺/H⁺ exchanger 3 in blood pressure regulation and angiotensin II-induced hypertension.

ABSTRACT: 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.

SUBMITTER: Li XC 

PROVIDER: S-EPMC6485378 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature