Combined administration of V1 and V2 receptor antagonists (OPC-21268 and OPC-31260) showed supra-additive hemodynamic responses and additive renal and metabolic responses in dogs with heart failure.
Do oral AVP V1 and V2 receptor antagonists improve hemodynamics and renal function in a canine model of congestive heart failure?
Combined V1 and V2 receptor antagonism provides superior hemodynamic benefits compared to V1 antagonism alone in a canine model of heart failure.
Rapid right ventricular pacing could induce congestive heart failure in conscious dogs with significant increase in plasma concentration of arginine vasopressin (AVP) (from 1.2 +/- 0.2 to 3.4 +/- 0.6 pg/ml). In this experimental model of heart failure, oral administration of the selective AVP V1 receptor antagonist OPC-21268 significantly increased cardiac output and improved renal function without significant changes in serum electrolytes and hormones. Oral administration of the selective AVP V2 receptor antagonist OPC-31260 induced marked water diuresis, which resulted in significant increases in serum sodium concentration, plasma renin activity, and plasma concentration of AVP, although it did not produce hemodynamic improvement. Combined administration of OPC-21268 and OPC-31260 showed supra-additive hemodynamic responses as well as additive renal and metabolic responses, i.e., it showed prolonged decrease in mean arterial pressure and profound increase in cardiac output. These results suggest that AVP plays a significant role in elevation of vascular tone through V1 receptors and plays a major role in retaining free water through V2 receptors in this model of heart failure. Furthermore, combined administration of V1 and V2 receptor antagonists could induce not only metabolic and hormonal responses but also more beneficial hemodynamic responses than those observed following treatment with V1 receptor antagonist alone.
Naitoh et al. (Thu,) conducted a other in Congestive heart failure (experimental model). OPC-21268 and OPC-31260 (AVP V1 and V2 receptor antagonists) vs. Alone or baseline was evaluated on Hemodynamic, renal, and metabolic responses. Combined administration of V1 and V2 receptor antagonists (OPC-21268 and OPC-31260) showed supra-additive hemodynamic responses and additive renal and metabolic responses in dogs with heart failure.