Vasopressin antagonism in heart failure

Steven R. Goldsmith*, Mihai Gheorghiade

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

175 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1785-1791
Number of pages7
JournalJournal of the American College of Cardiology
Volume46
Issue number10
DOIs
StatePublished - Nov 15 2005

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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