STATE-OF-THE-ART PAPER
Vasopressin Antagonism in Heart Failure
Steven R. Goldsmith, MD*,* and
Mihai Gheorghiade, MD
* Hennepin County Medical Center, University of Minnesota, Minneapolis, Minnesota
Northwestern University Feinberg School of Medicine, Chicago, Illinois
Manuscript received November 5, 2004;
revised manuscript received February 7, 2005,
accepted February 14, 2005.
* Reprint requests and correspondence: Dr. Steven R. Goldsmith, Hennepin County Medical Center, University of Minnesota, 701 Park Avenue South, Orange 5, Minneapolis, Minnesota. (Email: srg_hcmc{at}yahoo.com).
Treatment of chronic heart failure (HF) is based on interference with the renin-angiotensin-aldosterone system and the adrenergic nervous system. Diuretics are used in volume-expanded patients. Insights from clinical trials and registries establish the need to consider correcting both cardiac loading conditions and nonload-related biological factors if HF therapy is to be optimized. Arginine vasopressin (AVP) represents a potentially attractive target for therapy in both acute and chronic HF. Excessive AVP secretion could contribute to both systolic and diastolic wall stress via V1a- and V2-mediated effects on the peripheral vasculature and on water retention. Arginine vasopressin also may directly and adversely affect myocardial function due to the effect of V1a activation on myocardial contractility and cell growth. Last, AVP may contribute to hyponatremia, a powerful predictor of poor outcome in HF. The development of effective nonpeptide antagonists to both the V1a and V2 receptors for AVP now allows for testing the hypotheses that interfering with AVP-mediated signaling could be beneficial in HF. This review summarizes the theoretical rationale for further development of such therapy, reviews the status of current compounds under development, and suggests key issues that need to be addressed as these agents undergo further clinical testing.
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Abbreviations and Acronyms
| | ADHF = acute decompensated heart failure | | AVP = arginine vasopressin | | HF = heart failure | | RAAS = renin-angiotensin-aldosterone system |
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