Pathogenesis of drug-resistant hypertension

More is known about the epidemiology of drug-resistant hypertension than particular pathogenic factors and pathways. Several recurring themes, however, seem evident on using insight from epidemiology and general knowledge of the pathophysiology of hypertension. Specifically, 4 main pathways converge on drug resistance including sodium handling, sympathetic nervous system activation, endothelial dysfunction, and arterial stiffness. These factors, and the various pathways and elements contributing to them, are reviewed. In addition to describing how these factors exert their individual influences on resistant hypertension, several examples of how interactions between these factors, particularly in the case of chronic kidney disease, are included. At the conclusion of this review some thoughts are offered on additional mechanisms and areas for potential research.