Effect of an oxytocin antagonist on plasma oxytocin levels during nocturnal uterine contractions in the pregnant baboon

Abstract

TT-235 is a potent oxytocin (OT) antagonist that blocks the action of OT at the receptor level. Previous studies have shown that pregnant baboons demonstrate nocturnal uterine contractions induced by OTas they near delivery. The purpose of this study was to evaluate the changes in plasma OT levels following uterine contraction blockage with TT-235. A tethered pregnant baboon model in its last trimesterof pregnancy was used. Three blocks of arterial blood samples, immediately before, plus 1 h and plus 2 h following an OT antagonist injection, were collected once nocturnal uterine contractions were detected.Each block consisted of a continuous 10 min withdrawal with 10 samples per block (1 ml/min). A TT-235 dosage of 300 μg/kg and saline for control were utilized. Uterine activities were monitoredas pressure changes in the amniotic fluid, and the frequency and mean amplitude of contractile activity per 10 min intervals were expressed as contractile force. Plasma OT levels were determined by a radioimmunoassayfollowing plasma extraction with petroleum ether. The contractile force was decreased by 77% (p < 0.05) within 2 h after TT-235 administration while it increased 23% following saline infusion.Plasma OT levels were unchanged following saline infusion while they increased 82% (p < 0.05) 2 h after the administration of TT-235. If a positive feedback existed between uterine contractionsand OT release, one would expect plasma OT levels to be decreased with contractile activity following TT-235 infusion. Since this is not the case in the present study, the data suggest that there is eithera negative feedback or an independent relationship between nocturnal uterine contractions and OT release.