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ENaC in Salt-Sensitive Hypertension: Kidney and Beyond
Ashley L Pitzer1, Justin P Van Beusecum1, Thomas R Kleyman2
1Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, 2215 Garland Avenue, P415C Medical Research Building IV, Nashville, TN, 37232, USA.
Purpose Of Review:
The main goal of this article is to discuss the role of the epithelial sodium channel (ENaC) in extracellular fluid and blood pressure regulation.
Recent Findings:
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.
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The kidneys are bean-shaped organs located in the retroperitoneal space, on either side of the vertebral column, between the T12 and L3 vertebrae. They are partially protected by the rib cage and surrounded by perirenal fat, which provides cushioning. They are responsible for urine formation and play critical roles in regulating blood pressure, electrolyte levels, and hormone production. The ureters...
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