Epithelial sodium channels and hypertension

Abstract

The epithelial Na channel (ENaC) mediates Na absorption in the most distal segments of the nephron, and has an important role in the regulation of extracellular fluid volume and blood pressure. Rare ENaC gain‐of‐function mutations have been described in an inherited form of hypertension, and rare loss‐of‐function mutations result in hypotension. ENaC polymorphisms associated with modest gains‐of‐function have been described. Whether these polymorphisms contribute to hypertension in selected populations remains to be determined. A number of factors influence ENaC function and may contribute to increases in ENaC activity under certain conditions. Proteolytic cleavage of ENaC at specific sites results in channel activation by releasing inhibitory tracts imbedded within the channel's alpha and gamma subunits. In certain pathologic states, enhanced ENaC cleavage may result in channel activation, renal Na retention and hypertension. For example, in the setting of nephrotic syndrome filtered plasminogen is converted to plasmin, which can cleave and activate the channel. (Supported by DK054354, DK065161 and DK079307)