Most recently, the endothelial surface layer facing the blood stream has become a focus of interest [46
]. This soft layer, termed endothelial glycocalyx, is a negatively charged biopolymer known to preferentially bind sodium [55
]. It has been calculated that about 700 mg of sodium can be transiently bound to the endothelial glycocalyx in the human body, which is about the amount contained in a single meal [10
]. Interestingly, the sodium buffering capacity of the endothelial glycocalyx is severely damaged by excessive sodium intake over time, leading to a significant reduction of the negatively charged heparan sulphate residues in the endothelial glycocalyx [56
These observations led to a new concept of vascular sodium permeability, namely that two (more or less) permeable barriers determine the rate of sodium elimination after a salty meal [10
]. One barrier is the endothelial plasma membrane, with a variable sodium permeability depending on the abundance of epithelial sodium channels. The other barrier, located on the surface of the endothelium, is the endothelial glycocalyx that transiently buffers ingested sodium [55
] and, thus, controls access to the epithelial sodium channels (). Sodium channel activity and glycocalyx function are inversely related to each other. A plasma sodium concentration in the high-physiological range (>140 mM) reduces the negatively charged heparan sulphate residues of the endothelial glycocalyx [56
], increasing the amount of sodium reaching the endothelial sodium channels, which in turn makes the channels more active [34
]. The overall effect is that the barrier against sodium entry fails under these conditions and the endothelium becomes more permeable to sodium ().
Model explaining low vascular sodium sensitivity
Model explaining high vascular sodium sensitivity
As indicated above, evidence for a salt-sensitive endothelial glycocalyx and its relationship to endothelial epithelial sodium channels is based on in vitro
experiments and, at best, on ex vivo
studies in human tissue (e.g. human umbilical veins). To our knowledge, there are no direct studies in humans. However, if aldosterone is viewed as a hormone that facilitates sodium retention and epithelial sodium channel expression in the vascular endothelium [14
], then a link between salt and glycocalyx, albeit indirect, becomes visible. Clinical research often describes potentially important phenomena in the human without a mechanistic model. In this case, a mechanistic model based on in vitro
experiments is available first, and it will be up to clinical research to test it in the human.