Role of V₁ receptors in the action of vasopressin on the baroreflex control of heart rate

Arginine vasopressin (AVP) elicits a larger decrease in heart rate for a given increase in arterial pressure than do other vasoconstrictors, but there is disagreement as to whether this results from an increase in baroreflex gain or a resetting of the baroreflex to a lower blood pressure. It is also unclear which type of vasopressin receptor mediates the action of vasopressin on the baroreflex. In the present study, the effects of vasopressin, selective vasopressin V₁ and V₂ receptor agonists, oxytocin, and a vasopressin V₁ receptor antagonist on the baroreflex control of heart rate were investigated in conscious, chronically prepared rabbits. Baroreflex curves were generated with intravenous infusions of phenylephrine and nitroprusside and analyzed using a four-parameter logistic model. Intravenous infusion of vasopressin at 5 ng · kg^-1 · min^-1 increased mean arterial pressure by 9 mmHg and decreased heart rate by 31 beats/min. The arterial pressure at the midrange of the baroreflex curve (BP₅₀) decreased from 75.9 ± 4.8 to 57.6 ± 1.7 mmHg (P < 0.01), indicating a shift of the baroreflex curve to a lower pressure, but the gain did not change significantly. The actions of vasopressin on blood pressure, heart rate, and BP₅₀ were completely blocked by pretreatment with d(CH₂)₅[Tyr(Me)²]AVP, a selective V₁ receptor antagonist. Infusion of [Phe²,Ile³,Orn⁸]AVP, a selective V₁ receptor agonist, produced cardiovascular effects similar to those of vasopressin and decreased the BP₅₀ of the baroreflex from 73.0 ± 2.2 to 63.8 ± 2.2 mmHg (P < 0.05). Neither deamino-[D-Arg⁸]AVP (DDAVP), a selective V₂ receptor agonist, nor oxytocin significantly altered blood pressure and heart rate or the BP₅₀ of the baroreflex. These results provide evidence that infusion of vasopressin in conscious rabbits resets the baroreflex control of heart rate to a lower pressure without increasing its gain and demonstrate that this action is mediated by vasopressin V₁ receptors.