Sodium: a wolf in sheep's clothing.

High blood pressure is the main cause of disease-related morbidity and mortality worldwide. It is virtually absent in populations that consume natural foods low in sodium. In other countries, however, where the individual intake of sodium is at least 10 times greater, the prevalence of arterial hypertension is about 40%. Vascular endothelium plays a central role in blood pressure regulation. In addition to the kidney, the vasculature is a major target for aldosterone where it controls nonexcitable sodium channels in the endothelium. High sodium channel expression/activity downregulates the release of nitric oxide (NO), and thus determines endothelial function. Mechanical cell stiffness is therefore the means whereby high sodium channel activity reduces NO release. We have found that small changes of plasma sodium, but only above 139 mM, and potassium above 4 mM regulate the stiffness of the submembrane actin web and thus control the shear stress-dependent activity of endothelial NO synthase, which lies directly beneath the cell membrane. Plasma sodium above 139 mM stiffens the actin web of the endothelial cell, and plasma potassium greater than 4 mM does the opposite. In conclusion, vascular endothelial cells are highly sensitive to changes in extracellular sodium and potassium but only within and above the normal range. This sensitivity may serve as a physiological feedback mechanism to regulate local blood flow. It becomes pathogenic, however, when the concentration of plasma sodium or potassium changes towards and beyond the upper limits of the normal range.