OXYTOCIN ANTAGONISTS DELAY THE INITIATION OF PARTURITION AND PROLONG ITS ACTIVE PHASE IN RATS

The physiological importance of oxytocin for the initiation and maintenance of labour and delivery is controversial. We investigated the effects of two novel peptide oxytocin antagonists on the onset and the progress ofdelivery in rats implanted with a jugular vein cannula one day before term. During delivery rats were given either an oxytocin antagonist (OVT16, n=10, or F382, n=7, 30 mu g/kg) or vehicle (n=10, 9) after the birth of the second pup and the time to deliver five more pups was recorded. Other rats were given an injection of F382 (30 mu g/kg, n=7) or vehicle (n=9) after the birth of the fourth pup and the time to deliver three more pups was recorded. In another experiment rats were given repeated injections of F382 (30 or 60 mu g/kg, n=13, 11) or vehicle (n=32) prepartum on the day of expected term and the time of onset and the progress of delivery was recorded. Rats given an antagonist after the second pup delivered the next five pups in 100 +/- 8 min (F382) and 83 +/- 12 min (OVT16), significantly slower than the respective controls (51 +/- 6 and 49 +/- 6 min, U-test, P<0.05). Four of the 7 rats given F382 after the fourth pup showed no prolongation of delivery (time between pups 4-7: 24.7 +/- 2.9 vs 27.5 +/- 3.1 min in controls), while in the other three rats delivery was prolonged (time between pups 4-7: 86 +/- 4.3 min). The onset of delivery was significantly delayed in rats given repeated injections of F382 at 60 mu g/kg on the afternoon of expected delivery but before labour had begun (median shift 14.5 h vs controls, U-test, P<0.05). These results suggest that in rats oxytocin is involved in both the initiation and the maintenance of parturition and that it is more important during the early rather than the later stages of delivery.