THE OXYTOCIN ANTAGONIST ATOSIBAN PREVENTS ANDROSTENEDIONE-INDUCED MYOMETRIAL CONTRACTIONS IN THE CHRONICALLY INSTRUMENTED, PREGNANT RHESUS-MONKEY

We tested the hypothesis that increased oxytocin is a necessary mechan ism for the mediation of androstenedione (Delta(4)A)-induced myometria l contractions by investigating the effects of maternal treatment with the oxytocin antagonist atosiban on in vivo Delta(4)A-induced contrac tions. In four monkeys (group I), maternal estradiol, oxytocin, and my ometrial contractions were assessed at baseline and after continuous i v Delta(4)A administration. Similar measurements were made in three mo nkeys (group II) that received the same Delta(4)A infusion regimen, bu t in addition were treated daily with atosiban. Maternal estradiol and oxytocin levels and contractions were also assessed in four additiona l monkeys (controls; group III), in which the Delta(4)A vehicle, intra lipid, was infused iv continuously. In group, I, Delta(4)A induced myo metrial contractions and increased maternal estradiol and oxytocin to term concentrations. No myometrial contractions occurred in group II m onkeys after combined Delta(4)A and atosiban treatment despite estradi ol being elevated to concentrations similar to those measured in group I monkeys. Atosiban had no effect on maternal heart rate or blood pre ssure. Maternal estradiol, oxytocin, and number of myometrial contract ions remained unchanged from baseline values in control monkeys. In co nclusion, oxytocin is a necessary part of the mechanisms mediating Del ta(4)A-induced myometrial contractions. Delta(4)A promotes myometrial contractions via similar mechanisms that mediate spontaneous term cont ractions in pregnant monkeys.