The (F)low Down on the Endothelial Epithelial Sodium Channel

Abstract

The epithelial sodium channel (ENaC) contributes to blood pressure homeostasis through renal salt and water transport; increases in ENaC activity increase salt and water reabsorption along the distal nephron, increasing extracellular fluid volume and blood pressure. The importance of tubular ENaC in cardiovascular homeostasis is manifested in Liddle’s disease and type I pseudohypoaldosteronism, diseases associated with the gain and loss of ENaC function, respectively. However, several recent studies suggest that ENaC proteins may play a more ubiquitous role in blood pressure control as mechanosensors. Because ENaC proteins are closely related to a family of mechanosensitive proteins in the nematode termed “degenerins,” several laboratories have addressed the potential role of ENaC proteins as mechanosensors.1–3 In addition to their role in salt and water homeostasis, ENaC proteins and their relatives, acid-sensing ion channels (ASICs), may contribute to control of blood pressure through reflex regulation of the autonomic nervous system (baroreflex, chemoreflex, and metaboreflex) and local control of vascular tone.1 Recent literature reviews suggest that ENaC proteins may function as sensors of pressure-induced vascular stretch and laminar flow.1–3 The role of ENaC as a mediator of pressure-induced constriction in certain vessels is supported by several investigations; however, the role of ENaC as a flow sensor remains unclear.1 Because of their evolutionary relationship to mechanotransduction in the nematode, several laboratories have suggested that ENaC channels may act as flow …