From the Department of Medicine (S.M.M., T.R.K.), University of Pittsburgh, PA.
Division of Clinical Pharmacology, Department of Medicine, and Department of Molecular Physiology and Biophysics Vanderbilt University, Nashville, TN (A.K.).
Hypertension. 2021 Mar 3;77(3):759-767. doi: 10.1161/HYPERTENSIONAHA.120.14481. Epub 2021 Jan 25.
The development of high blood pressure is influenced by genetic and environmental factors, with high salt intake being a known environmental contributor. Humans display a spectrum of sodium-sensitivity, with some individuals displaying a significant blood pressure rise in response to increased sodium intake while others experience almost no change. These differences are, in part, attributable to genetic variation in pathways involved in sodium handling and excretion. ENaC (epithelial sodium channel) is one of the key transporters responsible for the reabsorption of sodium in the distal nephron. This channel has an important role in the regulation of extracellular fluid volume and consequently blood pressure. Herein, we review the role of ENaC in the development of salt-sensitive hypertension, and present mechanistic insights into the regulation of ENaC activity and how it may accelerate sodium-induced damage and dysfunction. We discuss the traditional role of ENaC in renal sodium reabsorption and review work addressing ENaC expression and function in the brain, vasculature, and immune cells, and how this has expanded the implications for its role in the initiation and progression of salt-sensitive hypertension.
高血压的发展受遗传和环境因素的影响，其中高盐摄入是已知的环境因素之一。人类对盐的敏感性存在差异，一些人在摄入更多的钠后血压明显升高，而另一些人几乎没有变化。这些差异部分归因于钠处理和排泄途径中遗传变异。ENaC（上皮钠通道）是负责在远曲小管重吸收钠的关键转运体之一。该通道在调节细胞外液体积和血压方面起着重要作用。本文综述了 ENaC 在盐敏感性高血压发展中的作用，并介绍了 ENaC 活性调节的机制以及它如何加速钠诱导的损伤和功能障碍。我们讨论了 ENaC 在肾脏钠重吸收中的传统作用，并回顾了 ENaC 在大脑、血管和免疫细胞中的表达和功能的相关研究，这扩展了其在盐敏感性高血压的发生和进展中的作用。
