title: Salt overload damages the glycocalyx sodium barrier of vascular endothelium.
abstract: 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 (∼0.25 pN/nm) of the eGC on the luminal endothelial surface of split-open human umbilical arteries were quantified. In presence of aldosterone, the increase of extracellular sodium concentration from 135 to 150 mM over 5 days (sodium overload) led the eGC shrink by ∼50% and stiffening by ∼130%. Quantitative eGC analyses reveal that sodium overload caused a reduction of heparan sulphate residues by 68% which lead to destabilization and collapse of the eGC. Sodium overload transformed the endothelial cells from a sodium release into a sodium-absorbing state. Spironolactone, a specific aldosterone antagonist, prevented these changes. We conclude that the endothelial glycocalyx serves as an effective buffer barrier for sodium. Damaged eGC facilitates sodium entry into the endothelial cells. This could explain endothelial dysfunction and arterial hypertension observed in sodium abuse.
authors.affiliation: Institute of Physiology II, University of Münster, Robert-Koch-Str. 27b, 48149, Münster, Germany. oberlei@uni-muenster.de
authors.forename: Hans
authors.initials: H
authors.lastname: Oberleithner
authors.forename: Wladimir
authors.initials: W
authors.lastname: Peters
authors.forename: Kristina
authors.initials: K
authors.lastname: Kusche-Vihrog
authors.forename: Stefanie
authors.initials: S
authors.lastname: Korte
authors.forename: Hermann
authors.initials: H
authors.lastname: Schillers
authors.forename: Katrin
authors.initials: K
authors.lastname: Kliche
authors.forename: Kilian
authors.initials: K
authors.lastname: Oberleithner
mesh_terms: D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D019276:Glycocalyx / Q000187:drug effects* / Q000378:metabolism; D019763:Heparin Lyase / Q000502:physiology; D006801:Humans; D018625:Microscopy, Atomic Force; D012964:Sodium / Q000378:metabolism*; D012965:Sodium Chloride / Q000494:pharmacology*; D013148:Spironolactone / Q000494:pharmacology; D014469:Umbilical Arteries; D059289:Vascular Stiffness / Q000187:drug effects
chemical_list: D013148:Spironolactone; D012965:Sodium Chloride; D012964:Sodium; D019763:Heparin Lyase