Role of epithelial sodium channels (ENaCs) in endothelial function

Abstract

An increasing number of mechano-sensitive ion channels in endothelial cells (ECs) have been identified in response to blood flow and hydrostatic pressure. However, how these channels response to flow under different physiological and pathological conditions remains unknown. Our results showed that ENaCs were co-localized with hemeoxygenase-1 (HO-1) and hemeoxygenase-2 (HO-2) within the caveolae on the apical membrane of ECs and were sensitive to stretch pressure and shear stress. ENaCs kept low activities until their physiology environment was changed; in this case, the up-regulation of HO-1, which in turn facilitated heme degradation and hence increased the carbon monoxide (CO) generation. CO potently increased the bioactivity of ENaCs, releasing the channel from inhibition. Endothelial cells started to response to shear stress by increasing the Na+ influx rate. Elevation of [Na+]i hampered the transportation of L-arginine, resulting in impairing the nitric oxide (NO) generation. Our data suggested that ENaCs endogenous to human endothelial cells were mechano-sensitive. Persistent activation of ENaCs could inevitably lead to endothelium dysfunction and even vascular diseases such as atherosclerosis.