Evidence for a vasodilatory effect of vasopressin in the conscious rat.

Experiments were performed on conscious, chronically instrumented rats to determine the cardiovascular effects of intravenous arginine vasopressin (AVP) with and without V1-vasopressinergic antagonist administration. This design allowed the assessment of the cardiovascular effects of high circulating levels of AVP in the absence of the direct vasoconstrictor properties of the hormone. One group of rats (n = 10) were administered a constant infusion of AVP (2.5 mU/min iv) for 40 min and demonstrated increased mean arterial blood pressure (MABP) and total peripheral resistance (TPR), while heart rate (HR) and cardiac output (CO) fell. Another group of animals (n = 7) also received AVP for 40 min; however, at 25 min of the infusion, 10 micrograms/kg of d(CH2)5Tyr(Me)AVP was given intravenously. Administration of this V1-vasopressinergic antagonist caused MABP and TPR to fall below pre-infusion levels, although AVP infusion continued. HR and CO returned to control. Additional experiments showed no effect of the antagonist (n = 8) or AVP vehicle (n = 7) alone on the measured hemodynamic variables. In addition, pretreatment with the cyclooxygenase inhibitor meclofenamate did not affect the observed vasodilation in AVP-treated animals given the antagonist. A final group of animals (n = 6) was pretreated with d(CH2)5Tyr(Me)AVP prior to AVP infusion. On AVP administration, TPR fell in all animals. These data suggest that AVP exerts a vasodilatory effect unrelated to stimulation of V1-vasopressinergic receptors or arterial baroreceptors, which may partially offset the potent vasoconstrictor properties of this peptide.