From salt to sugar Unravelling the role of glycosaminoglycans in the sodium balance

This thesis aimed to investigate sodium-induced effects on blood pressure and osmolality beyond the traditional view in which osmotic equilibration is present between the intra- and extracellular space, and changes in plasma sodium concentration will induce water shifts between the intracellular and extracellular compartment. In the first part of this thesis, we addressed the presence of a third compartment for sodium accumulation in regulating blood pressure and osmoregulation. We demonstrate that the salt-sensitive blood pressure response cannot be explained by changes in fluid balance, but seems to coincide with incapacity for vasodilation and altered sympathovagal balance. In the following chapter, we show that patients' characteristics linked to tissue sodium accumulation play a crucial role in osmo(dys)regulation. Because previous studies have suggested an important role for negatively charged glycosaminoglycans in the regulation of tissue sodium accumulation, we aimed to unravel the role of glycosaminoglycan metabolism in blood pressure regulation and maintenance of the milieu interieur during sodium loading in the second part of this thesis. With epidemiological studies and randomised controlled sodium intervention trials, we demonstrate that disturbance of glycosaminoglycan synthesis (either genetically or due to disease) influences sodium homeostasis and salt sensitivity of blood pressure. Finally, we demonstrate that sodium accumulation in the placenta is important for maternal blood pressure regulation during pregnancy. Altogether, this thesis demonstrates that the sodium balance is far more complicated than previously assumed and that glycosaminoglycans play a crucial role in the complex and precise regulation of sodium.