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

The physiological importance of oxytocin for the initiation and mainte nance of labour and delivery is controversial. We investigated the eff ects of two novel peptide oxytocin antagonists on the onset and the pr ogress ofdelivery in rats implanted with a jugular vein cannula one da y before term. During delivery rats were given either an oxytocin anta gonist (OVT16, n=10, or F382, n=7, 30 mu g/kg) or vehicle (n=10, 9) af ter 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 we re given repeated injections of F382 (30 or 60 mu g/kg, n=13, 11) or v ehicle (n=32) prepartum on the day of expected term and the time of on set and the progress of delivery was recorded. Rats given an antagonis t after the second pup delivered the next five pups in 100 +/- 8 min ( F382) and 83 +/- 12 min (OVT16), significantly slower than the respect ive 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 deliv ery (time between pups 4-7: 24.7 +/- 2.9 vs 27.5 +/- 3.1 min in contro ls), while in the other three rats delivery was prolonged (time betwee n pups 4-7: 86 +/- 4.3 min). The onset of delivery was significantly d elayed in rats given repeated injections of F382 at 60 mu g/kg on the afternoon of expected delivery but before labour had begun (median shi ft 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 o f parturition and that it is more important during the early rather th an the later stages of delivery.