Salt Sensitivity of Blood Pressure and the Role of the Immune System in Hypertension

Salt-sensitive blood pressure is a clinical phenotype defined as exaggerated blood pressure responses to salt loading and salt depletion. This characteristic occurs in 25% of the general population and 50% of patients with hypertension and contributes to the pathogenesis of hypertension in some patients. Hypertension is associated with chronic inflammatory responses and has immune cell accumulation in several hypertensive target organs, including the brain, kidneys, heart, blood vessels, and the perivascular adipose tissue, and these cellular responses likely exacerbate hypertension. The different factors implicated in the pathogenesis of salt-sensitive hypertension include renin-angiotensin-aldosterone system dysfunction, aldosterone-dependent and aldosterone-independent mineralocorticoid receptor signaling, and the sympathetic nervous system dysfunction. Experimental studies have shown an important role of both innate and adaptive immune cells, especially lymphocytes, in angiotensin II-induced hypertension. The epithelial sodium channel (ENaC) allows entry of sodium into dendritic cells, and this leads to a sequence of events, including the production of reactive oxygen species, which activates the NLRP3 inflammasome and contributes to salt-sensitive hypertension through the amiloride-sensitive ENaC and isolevuglandin-adduct formation. This review summarizes the general aspects of salt sensitivity, focuses on the immunological/inflammatory factors involved in its development, considers general changes in microvasculature, and discusses management.