Arginine vasopressin receptor signaling and functional outcomes in heart failure

- Circulating AVP is elevated in HF patients, which is associated with increased morbidity and mortality.
- Chronic AVP signaling via V1AR and V2R leads to increased cardiac hypertrophy and renal water reabsorption, respectively.
- V2R-selective antagonists reduce water reabsorption, but increase AVP levels and mortality in HF patients.
- Cardiac V1AR expression is increased two-fold in HF patients, results replicated in both small and large animal models of HF.
- Chronic V1AR signaling promotes cardiac remodeling, βAR desensitization and contractile dysfunction.
- These effects are reversed by V1AR blockade, providing rationale for targeting this system as a therapeutic approach for HF.