Uterine and placental prostaglandins and their modulation of oxytocin sensitivity and contractility in the parturient uterus.
The parturient uterus develops a markedly enhanced sensitivity to the uterotonic action of oxytocin (OT). The mechanism leading to this enhanced OT sensitivity is not known. Our previous work suggested that prostaglandins (PGs) may be involved. To define the relationship between OT sensitivity and uterine PG production, we measured uterine sensitivity to OT by a quantitative dose-response procedure in rats on Days 19, 20, 21 and 22 of pregnancy and monitored uterine and placental tissue concentrations of PGF2 alpha and PGE2. In addition, we determined the effects of inhibition of endogenous PG synthesis on OT sensitivity and uterine contractility. We found that both OT sensitivity and spontaneous contractility are positively related to uterine PGF2 alpha production. An abrupt increase in OT sensitivity was observed on Days 21 and 22 of pregnancy. The increase in OT sensitivity was coincidental with the marked increase in PGF2 alpha production in the uterus on Days 21 and 22 of pregnancy. Suppression of in vivo PG synthesis caused a reduction in both spontaneous uterine contractility and OT-induced contractions. Uterine PGE2 concentrations and release were 3-5 times lower than PGF2 alpha. There were no significant fluctuations of uterine PGE2 concentration measured on these last 4 days of gestation. Placental PG levels were also found not to be related to uterine contractility. Placental PGE2 levels were higher than PGF2 alpha and may play a regulatory role in placental perfusion. However, placental PGs did not vary with gestational age.
D000818:Animals; D004008:Diclofenac / Q000494:pharmacology; D015237:Dinoprost; D005260:Female; D007743:Labor, Obstetric; D010121:Oxytocin / Q000494:pharmacology*; D010920:Placenta / Q000032:analysis*; D011247:Pregnancy; D011453:Prostaglandins / Q000032:analysis / Q000502:physiology*; D011460:Prostaglandins F / Q000502:physiology; D051381:Rats; D014590:Uterine Contraction / Q000187:drug effects*; D014599:Uterus / Q000032:analysis*
D011453:Prostaglandins; D011460:Prostaglandins F; D004008:Diclofenac; D010121:Oxytocin; D015237:Dinoprost