The endothelial aENaC contributes to vascular endothelial function in vivo

The Epithelial Sodium Channel (ENaC) is a key player in renal sodium homeostasis. The expression of alpha beta gamma ENaC subunits has also been described in the endothelium and vascular smooth muscle, suggesting a role in vascular function. We recently demonstrated that endothelial ENaC is involved in aldosterone-modulated endothelial stiffness. Here we explore the functional role of the endothelial aENaC subunit in vascular function in vivo. Compared to littermates, mice with conditional aENaC subunit gene inactivation in the endothelium only (endo-aENaC Knock Out mice) had no difference in their physiological parameters such as systolic blood pressure or heart rate. Acute and long-term renal Na+ handlings were not affected, indicating that endothelial aENaC subunit is not involved in renal sodium balance. Pharmacological inhibition of ENaC with benzamil blunted acetylcholine-induced nitric oxide production in mesenteric arteries from wild type mice but not in endo-aENaC(KO) mice, suggesting a critical role of endothelial ENaC in agonist-induced nitric oxide production. In endo-aENaC(KO) mice, compensatory mechanisms occurred and steady state vascular function was not altered except for flow-mediated dilation. Our data suggest that endothelial aENaC contributes to vascular endothelial function in vivo.