Time and technology will tell: the pathophysiologic basis of neurohormonal modulation in heart failure.

The central roles of neurohormonal abnormalities in the pathobiology of heart failure have been defined in recent decades. Experiments have revealed both systemic involvement and intricate subcellular regulation by circulating effectors of the sympathetic nervous system, the renin-angiotensin-aldosterone system, and others. Randomized clinical trials substantiated these findings, establishing neurohormonal antagonists as cornerstones of heart failure pharmacotherapy, and occasionally offering further insight on mode of benefit. This review discusses the use of β-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and aldosterone receptor antagonists in the treatment of heart failure, with particular attention to the pathophysiologic basis and mechanisms of action.