Is too much neurohormonal blockade harmful?
A number of neurohormones and cytokines are activated in heart failure and their activity is related to the progression of heart failure. Inhibiting the deleterious effects of the activated sympathetic and the renin-angiotensin-aldosterone systems with b-blockers, angiotensin-converting enzyme inhibitors, and aldosterone blockers has been remarkably successful in improving the survival of patients with heart failure. However, inhibition of the other neurohormones and cytokines has not provided the expected incremental benefit, and in some cases has been deleterious, suggesting a ceiling effect of further neurohormonal blockade. This article reviews some of these studies and analyzes the possible causes of these observations.
Anand
Inder S
IS
VA Medical Center, One Veterans Drive, 111-C, Minneapolis, MN 55417, USA. anand001@umn.edu
D057911:Angiotensin Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D016207:Cytokines / Q000037:antagonists & inhibitors; D004359:Drug Therapy, Combination; D016232:Endothelins / Q000037:antagonists & inhibitors; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006727:Hormone Antagonists / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors*; D012084:Renin-Angiotensin System / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D016207:Cytokines; D016232:Endothelins; D006727:Hormone Antagonists; D018377:Neurotransmitter Agents