Blood pressure regulation via the epithelial sodium channel: From gene to kidney and beyond

1. The epithelial sodium channel (ENaC) has long been recognized as playing a vital role in blood pressure (BP) regulation due to its involvement in fluid balance. The genes encoding the three ENaC subunits are likewise important contributors to hypertension, both in rare monogenic diseases and in the general population. 2. The unusually high numbers of genetic variants associated with complex traits, including BP, that are located in non-coding areas suggest an involvement of these variants in regulatory functions. This may involve differential regulation of expression in different tissues. 3. Emerging evidence indicates that the ENaC plays an important role in BP determination not only via its actions in the kidney, but also in other tissues commonly involved in BP regulation. The ENaC in the central nervous system is proposed to regulate BP via sympathetic nervous system activity. Recent evidence suggests that the ENaC contributes to vascular function and the myogenic response. Additional roles potentially include initiation of the baroreceptor reflex via ENaC in the baroreceptors and driving high salt intake with a 'taste for salt' via ENaC in the tongue. 4. The present review describes the involvement of the ENaC in the determination of BP at a genetic and physiological level, detailing recent evidence for its role in the kidney and in other pertinent tissues.