Mechanisms of sodium-mediated injury in cardiovascular disease: old play, new scripts

There is a strong association between salt intake and cardiovascular diseases, particularly hypertension, on the population level. The mechanisms that explain this association remain incompletely understood and appear to extend beyond blood pressure. In this review, we describe some of the 'novel' roles of Na⁺ in cardiovascular health and disease: energetic implications of sodium handling in the kidneys; local accumulation in tissue; fluid dynamics; and the role of the microvasculature, with particular focus on the lymphatic system. We describe the interplay between these factors that involves body composition, metabolic signatures, inflammation and composition of the extracellular and intracellular milieus.