Cardiovascular effects of dynorphin A-(1-13) and arginine vasopressin in fetal lambs

The cardiovascular effects of the kappa-opioid receptor agonist, dynorphin A-(1-13) (D13), were compared with those of arginine vasopressin (AVP) in intact and bilaterally vagotomized (VGX) fetal lambs. Intravenous injection of AVP (114 ng/kg) produced a significant rise in mean arterial pressure (MAP) lasting 15-20 min in both intact and VGX lambs. AVP produced a bradycardia in intact fetuses concurrently with the MAP response and had no effect on heart rate (HR) in VGX fetuses. D13 (500 micrograms/kg) also produced significant increases in MAP in intact and VGX fetuses that lasted 45-60 min. D13 produced a bradycardia in intact fetal lambs but, unlike AVP, significantly increased HR in VGX fetuses. HR responses to D13 had time courses similar to MAP responses in both intact and VGX fetal lambs. Pretreatment with a vasopressin V1-receptor antagonist significantly attenuated pressor responses to AVP in both treatment groups and to D13 in intact fetuses and abolished the D13 pressor response in VGX fetuses. The antagonist also completely blocked HR responses to AVP in intact and to D13 in VGX fetuses and attenuated the D13 HR response in intact fetuses. Therefore the effects of D13 on ovine fetal cardiovascular function appear to be mediated in part through AVP pathways. D13 also appears to have a positive chronotropic effect on the heart that is normally masked by inhibitory vagal activity.