Attenuation of PGF2alpha release in ewes infused with the oxytocin antagonist L-368,899.
We have investigated the effects of systemic administration of the oxytocin antagonist (OTA) L-368,899 on luteolytic PGF(2alpha) release in ewes. In the first study, carried out in four ovariectomized ewes primed with progesterone to induce responsiveness to oxytocin, 3-h i.v. infusions of 3, 10 and 30 microg/kg/min OTA, carried out on days 12, 14, 16 and 18 in a Latin Square design, resulted in a significant attenuation of the oxytocin induced increase in PGFM concentration at all doses (OTA 139+/-8.3% of pre-oxytocin baseline; control 206.8+/-18.7%; P<0.005). In a further study, continuous infusion of cyclic ewes (n=6) with 10 microg/kg/min OTA from day 13 to day 17 of the cycle resulted in a reduction in both the frequency (OTA 1.0+/-0.4/ewe; control 2.2+/-0.2/ewe; P<0.05) and amplitude (OTA 31.8+/-11.0 pg/ml; control 68.8+/-10.4 pg/ml; P<0.05) of endogenous PGFM episodes compared to control ewes (n=5) measured during daily 8-h sampling windows on days 14-17. This reduction in PGFM concentrations was accompanied by a modest extension in the day of luteolysis (progesterone <0.5 ng/ml) to day 17.5+/-0.4 in the OTA treated group compared with day 16.4+/-0.5 in the control group (P=0.07). The results demonstrate that treatment with OTA caused a significant reduction in episodes of increased PGFM concentration during the period of luteolysis and may provide an approach by which to reduce early pregnancy failure.
Mann
G E
GE
Division of Animal Physiology, School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, LE12 5RD, UK. George.Mann@Nottingham.ac.uk
Lamming
G E
GE
Scholey
D
D
Hunter
M
M
Pettibone
D J
DJ
D000818:Animals; D001892:Camphanes / Q000494:pharmacology*; D003338:Corpus Luteum / Q000187:drug effects; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D030762:Estrous Cycle / Q000097:blood; D005260:Female; D003341:Luteolysis / Q000187:drug effects*; D010121:Oxytocin / Q000037:antagonists & inhibitors*; D010879:Piperazines / Q000494:pharmacology*; D011374:Progesterone / Q000097:blood; D011863:Radioimmunoassay / Q000662:veterinary; D012756:Sheep / Q000502:physiology*; D014599:Uterus / Q000378:metabolism
D001892:Camphanes; D010879:Piperazines; C008228:15-keto-13,14-dihydroprostaglandin F2alpha; D011374:Progesterone; D010121:Oxytocin; D015237:Dinoprost; C086206:L 368899