Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, 2215 Garland Avenue, P415C Medical Research Building IV, Nashville, TN, 37232, USA.
Departments of Medicine, Cell Biology, Pharmacology, and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA.
Curr Hypertens Rep. 2020 Aug 27;22(9):69. doi: 10.1007/s11906-020-01067-9.
The main goal of this article is to discuss the role of the epithelial sodium channel (ENaC) in extracellular fluid and blood pressure regulation.
Besides its role in sodium handling in the kidney, recent studies have found that ENaC expressed in other cells including immune cells can influence blood pressure via extra-renal mechanisms. Dendritic cells (DCs) are activated and contribute to salt-sensitive hypertension in an ENaC-dependent manner. We discuss recent studies on how ENaC is regulated in both the kidney and other sites including the vascular smooth muscles, endothelial cells, and immune cells. We also discuss how this extra-renal ENaC can play a role in salt-sensitive hypertension and its promise as a novel therapeutic target. The role of ENaC in blood pressure regulation in the kidney has been well studied. Recent human gene sequencing efforts have identified thousands of variants among the genes encoding ENaC, and research efforts to determine if these variants and their expression in extra-renal tissue play a role in hypertension will advance our understanding of the pathogenesis of ENaC-mediated cardiovascular disease and lead to novel therapeutic targets.
本文的主要目的是讨论上皮钠离子通道（ENaC）在细胞外液和血压调节中的作用。
除了在肾脏中对钠处理的作用外，最近的研究还发现，在包括免疫细胞在内的其他细胞中表达的 ENaC 可以通过肾外机制影响血压。树突状细胞（DC）通过 ENaC 依赖性方式被激活并有助于盐敏感性高血压。我们讨论了最近关于 ENaC 在肾脏和其他部位（包括血管平滑肌、内皮细胞和免疫细胞）的调节方式的研究。我们还讨论了这种肾外 ENaC 如何在盐敏感性高血压中发挥作用及其作为新型治疗靶点的潜力。ENaC 在肾脏中对血压调节的作用已得到充分研究。最近的人类基因测序工作已经在编码 ENaC 的基因中鉴定出数千种变体，研究工作旨在确定这些变体及其在肾外组织中的表达是否在高血压中发挥作用，这将增进我们对 ENaC 介导的心血管疾病发病机制的理解，并为新型治疗靶点提供依据。
