Feedforward activation of endothelial ENaC by high sodium.

Kidney epithelial sodium channels (ENaCs) are known to be inactivated by high sodium concentrations (feedback inhibition). Recently, the endothelial sodium channel (EnNaC) was identified to control the nanomechanical properties of the endothelium. EnNaC-dependent endothelial stiffening reduces the release of nitric oxide, the hallmark of endothelial dysfunction.

Firewall function of the endothelial glycocalyx in the regulation of sodium homeostasis.

Plasma sodium, slightly above normal and in presence of aldosterone, stiffens vascular endothelium and reduces nitric oxide release with the consequence of endothelial dysfunction. This process is mediated by epithelial sodium channels (ENaC) and, most likely, the endothelial Na(+)/K(+)-ATPase. Both, ENaC and Na(+)/K(+)-ATPase, are located in the plasma membrane of endothelial cells and embedded in the endothelial glycocalyx (eGC).

Salt overload damages the glycocalyx sodium barrier of vascular endothelium.

Sodium overload stiffens vascular endothelial cells in vitro and promotes arterial hypertension in vivo. The hypothesis was tested that the endothelial glycocalyx (eGC), a mesh of anionic biopolymers covering the surface of the endothelium, participates in the stiffening process. By using a mechanical nanosensor, mounted on an atomic force microscope, height (∼400 nm) and stiffness (∼0.