Sodium balance and hypertension: rare genetic disorders expose pathogenic mechanisms

The importance of sodium in the pathophysiology of hypertension has been revealed by several sources, including large epidemiological analyses, interventional trials, and a large body of experimental and clinical evidence. According to Guyton's hypothesis, a shift of the pressure-natriuresis curve has been described in all forms of hypertension, suggesting that the ability of the kidney to excrete sodium must be altered in hypertension. Yet, the intrarenal mechanism responsible for the abnormal salt excretion remains unknown. In recent years, the discovery of the molecular mechanisms involved in the pathogenesis of some rare forms of hypertension, i.e. , Liddle's syndrome, glucocorticoid-remediable hypertension, and apparent mineralocorticoid excess, has revived the interest in salt-induced hypertension, since the reported genetic defects decrease the ability of the kidneys to excrete sodium. This review presents the pathogenic mechanisms revealed by these rare disorders and discusses the possible implication of these discoveries for the understanding of the pathophysiology of essential hypertension.