title: The epithelial Na+ channel: a new player in the vasculature.
abstract: OBJECTIVE
  Approximately 20 years ago, a paradigm shift occurred questioning whether expression of the epithelial Na⁺ channel (ENaC) was mainly restricted to epithelial tissues. In this review, the recent findings of ENaC regulation, and its potential contributions to the function and dysfunction of the vasculature, is discussed.
  
  
  RESULTS
  Over the last few years, the expression, localization, and functional properties of ENaC have been determined in the two main vascular cell types: endothelial cells, and vascular smooth muscle cells. A chronically increased ENaC membrane abundance can lead to endothelial stiffening and to a reduced release of nitric oxide, the hallmark of endothelial dysfunction. Endothelial ENaC was shown to determine vasoconstriction by negatively modulating nitric oxide release in mesenteric arteries, likely via the PI3K/Akt signaling pathway. ENaC has therefore been recognized as a potentially important regulator of vascular nanomechanics and as a transducer of mechanical forces.
  
  
  CONCLUSIONS
  As ENaC expression is broader than anticipated, it has become clear that the protein may play a crucial role in the vasculature as it is located at the interface between blood and tissue, and is therefore implicated in the development of endothelial dysfunction and hypertension.
authors.affiliation: aInstitute of Physiology II, University of Münster, Münster, Germany bINSERM U872 Team 1, Centre de Recherche des Cordeliers, Université René Descartes, Université Pierre et Marie Curie Paris, Paris Cedex 06, France.
authors.forename: Kristina
authors.initials: K
authors.lastname: Kusche-Vihrog
authors.forename: Antoine
authors.initials: A
authors.lastname: Tarjus
authors.forename: Johannes
authors.initials: J
authors.lastname: Fels
authors.forename: Frédéric
authors.initials: F
authors.lastname: Jaisser
mesh_terms: D000818:Animals; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000503:physiopathology; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology; D040542:Mechanotransduction, Cellular; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000503:physiopathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D013314:Stress, Mechanical
chemical_list: D053503:Epithelial Sodium Channels; D009569:Nitric Oxide; D012964:Sodium; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt