Oxytocin antagonist blocks the vasodepressor but not the vasopressor effect of neurohypophysial peptides in chickens

Abstract

Cockerels with permanent cannulas in the brachial artery and vein were put into isolated slings. Arterial pressure and heart rate were continuously recorded. Following habituation, tests were initiated. In each cockerel 2 nmol/kg of the tested neurohypophysial peptide (NPs) or analogue was IV injected six times at 6-min intervals. Arginine vasotocin (AVT) caused an immediate vasodepressor (VDP) effect and tachycardia. These subsided within 20–30 s and were followed by a vasopressor (VP) response and bradycardia. On repeated injections of AVT, the VDP response declined and bradycardia intensified. Arginine vasopressin (AVP), oxytocin (OT), and mesotocin (MT) had short-lasting VDP effect in the following order of potency: OT = MT > AVT > AVP . Only AVT and, more effectively, AVP, caused a VP response. The VDP effect of MT and OT declined on repeated injections. When AVT was injected after three injections of MT, it had mostly an immediate VP effect. Although the V 1 agonist is VP in chickens, at the dose used the V 1 antagonist, [d(CH 2) 5,O-Me-Tyr 2]AVP, had no effect on cardiovascular responses to AVT. Pretreatment with OT antagonist, [d(CH 2) 5-O-Me-Tyr 2,Thr 4,Tyr 9,Orn 8]VT, abolished the VDP effect of all NPs. Thus, MT had no effect on blood pressure, whereas AVP and, more effectively, AVT, had a marked immediate VP action. In chickens the VDP effect of NPs is probably mediated by an OT/MT-like receptor, wherein the peptide's ring structure, shared by AVT, OT, and MT, is important. The VP effect is mediated by a receptor only partially similar to the mammalian V 1 receptor, where arginine in position 8, shared only by AVT and AVP, is necessary for action, and the native AVT is more effective than the mammalian AVP. This receptor reacts to the V 1 agonist but probably not to the V 1 antagonist.