Sodium-induced changes of the endothelial surface layer and microcirculation

Reduction of sodium intake has been recognized as a target for improvement of global health and lowering of medical costs. However, this target has not been met in any country and the optimum of maximum daily sodium intake remains controversial. Furthermore, it is also not fully understood how sodium loading leads to increased blood pressure and increased risk of cardiovascular events, and why the blood pressure response following sodium loading is so heterogeneous among individuals. We propose that sodium-associated microcirculatory changes might explain the - not yet clarified - link between sodium and high blood pressure. This thesis illustrates that our knowledge regarding sodium in (cardiovascular) health and disease continues to be challenged. We have challenged the classical two compartment view on sodium and volume homeostasis (chapter 2) and we have demonstrated that healthy volunteers are able to osmotically inactivate sodium following saline infusion (chapter 3). Furthermore, we have shown that both a dietary sodium load and an acute intravenous sodium load have damaging effects on the endothelial surface layer and microcirculation, independent of blood pressure (chapter 4 and chapter 5). We propose that sulodexide, a mixture of constituents of the endothelial surface layer, might be a new interesting drug to lower blood pressure (chapter 6). Our studies provide new insights into the relation between sodium, endothelial surface layer and microcirculation and are relevant for patients with hypertension, volume overload (e.g. patients with kidney disease, heart failure, dialysis patients) and dysnatriemia.