Myometrial oxytocin receptors and prostaglandin in the parturition process in the rat.
Parturition in rats is associated with an abrupt and marked increase in myometrial oxytocin (OT) receptor concentrations. In this study, we investigated the role of myometrial OT receptors in the initiation and the process of parturition. We produced chronic OT receptor blockade during the last 3 days of gestation by administration of a specific OT antagonist at 100 micrograms/day and 300 micrograms/day. We also suppressed OT receptor formation by inhibiting prostaglandin synthesis with naproxen sodium at 2 mg/day and 5 mg/day. We found that chronic blockade of OT receptors inhibited the uterotonic response to OT in Day 22 and Day 23 pregnant rats in a dose-dependent manner. OT antagonist treatment did not prolong the gestation period. However, the duration of parturition, fetal mortality, and the mortality incidence were increased in rats treated with the high dose of the OT antagonist compared to controls. Naproxen sodium at both dosage levels prolonged gestation by 24 h or longer, doubled the duration of parturition, and markedly increased fetal mortality and mortality incidence. Combined OT antagonist and naproxen treatment produced adverse outcomes similar to that produced by naproxen treatment alone. Myometrial OT receptor concentrations were markedly increased in all rats immediately postpartum, ranging from 210 to 425 fmol/mg protein compared to the 50 to 100 fmol/mg found in Day 21 and Day 22 pregnant rats. Correlation analyses between OT receptor concentrations and various parameters associated with gestation and parturition showed that there was a correlation between low OT receptor concentrations and long gestation period, prolonged parturition, and high fetal mortality rate.(ABSTRACT TRUNCATED AT 250 WORDS)
Chan
W Y
WY
Department of Pharmacology, Cornell University Medical College, New York, New York 10021.
Chen
D L
DL
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D005260:Female; D005313:Fetal Death / Q000139:chemically induced; D005865:Gestational Age; D007743:Labor, Obstetric / Q000378:metabolism*; D009215:Myometrium / Q000378:metabolism*; D010121:Oxytocin / Q000031:analogs & derivatives / Q000494:pharmacology; D011247:Pregnancy; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000378:metabolism*; D018045:Receptors, Oxytocin; D014590:Uterine Contraction / Q000187:drug effects / Q000502:physiology
D057911:Angiotensin Receptor Antagonists; D011453:Prostaglandins; D011945:Receptors, Angiotensin; D018045:Receptors, Oxytocin; C064578:oxytocin, Pen(1)-(4-MePhe)(2)-Thr(4)-Orn(8)-; D010121:Oxytocin