Purpose of review
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.
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.
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.