Figure 2. EnENaC limits NO production in the setting of high [Na⁺] and aldosterone.

ECs have a thick surface glycocalyx that limits the availability of Na⁺ for ENaC-dependent Na⁺ transport. The glycocalyx also enhances the endothelial response to shear stress, inducing an increase in intracellular Ca²⁺, activation of eNOS, NO production and vasodilation. Increased extracellular [Na⁺] leads to glycocalyx breakdown and enhanced Na⁺ entry via ENaC. An increase in the intracellular [Na⁺] stabilizes F-actin filaments, increasing the density of the cortical cytoskeleton and limiting cellular deformation. This events inhibit eNOS and NO production, leading to vascular dysfunction. Activation of MR by aldosterone in ECs increases ENaC expression, stabilizing the cytoskeleton and reducing deformability.