Sodium-induced inflammation-an invisible player in resistant hypertension

The purpose of this review was to discuss the role of sodium and inflammation in the pathophysiology of hypertension and the observed different hemodynamic effects of drugs. The Pathway-2 study revealed that similar reductions in vascular resistance after spironolactone and doxazosin resulted in opposite effects on sodium balance, water retention, and hemodynamic parameters. These and other clinical findings were bridged to recent experimental and physiological data. Tissue sodium accumulation in salt-sensitive individuals due to endothelial glycocalyx dysfunction causes macrophage infiltration, vascular inflammation, and local changes in angiotensin-2 and aldosterone concentrations. This inflammatory cascade leads to factor XII-related coagulation disorders with neutrophil extracellular trap formation (NETosis). This model of sodium-induced microcirculation impairment was used to explain the differences in central hemodynamic parameters after spironolactone or doxazosin treatment in resistant hypertension. Hypertension treatment by induced sodium removal or reduced sodium intake should reduce endothelial glycocalyx dysfunction, inflammation, NETosis, and coagulation disorders, leading to improved vascular health and cardiac diastolic function.