Because effective antagonists of both the V1a and V2 receptors are now available, several key issues must be considered in their future development. Clearly, both V1a- and V2-mediated effects are demonstrable in severe and/or decompensated HF; therefore it is reasonable to consider either or both types of antagonists in these settings. A pure V1a antagonist might produce arterial vasodilation, acute hemodynamic improvement, and, chronically, a reduced afterload-related stimulus to ventricular remodeling. It might also diminish venoconstriction and adverse direct myocardial stimulation from AVP. All V1a effects may be more important in the setting of other neurohormonal antagonists. However, if plasma AVP levels rose in the presence of a competitive V1a antagonist, unwanted water retention could occur, with either congestion or hyponatremia or both as a consequence. On the other hand, while a pure V2 antagonist will produce a sustained aquaresis, if AVP levels increased in response to the presence of a competitive antagonist, or due to increased osmolality, unwanted acute vasoconstriction and/or direct myocardial stimulation from V1a activation might occur.