The effects of indomethacin on uterine activity and prostaglandin (PG) concentrations during labor induced by administering ACTH to fetal sheep.

Abstract

To assess the importance of endogenous prostaglandins in parturition, we have examined the effects of indomethacin on maternal steroid concentrations and on the frequency and maximum amplitude of uterine contractions during delivery induced by administering adrenocorticotrophic hormone (ACTH) to fetal sheep. Uterine contractions were evaluated by measuring amniotic fluid pressure in chronically catheterized sheep, 130-days pregnant treated for 70 h with continuous infusions of intrafetal ACTH1–24, and with indomethacin or vehicle into the maternal femoral vein. Maternal plasma progesterone and estrone concentrations and fetal plasma Cortisol concentrations were estimated by radioimmunoassays (RIAs). Concentrations of prostaglandin E (PGE), PGF, and 6-oxoPGF1α (the hydrolysis product of PGI2) were measured by RIAs in myometrium, endometrium, cotyledons, amnion, and chorioallantois at different locations of the uterus. Labor was initiated after 70 h intrafetal ACTH treatment as indicated by a significant fall in maternal progesterone (P4) and rises in maternal plasma estrone (E1) and fetal plasma Cortisol concentrations, and by increased frequency and maximum amplitude of uterine contractions. indomethacin treatment had no significant effect on maternal plasma P4 or E1. Prostaglandin (PG) concentrations within uterine tissues varied with different uterine areas. However, overall, indomethacin significantly decreased concentrations of all PGs in all tissues examined, except for PGE in myometrium and endometrium. Indomethacin administration reduced the degree of cervical softening. After ACTH infusion alone there was an increase in the frequency and maximum amplitude of uterine contractions. In animals receiving concomitant indomethacin the frequency, but not the maximum amplitude of contractions, was significantly decreased. These results suggest that PGs play a role in the regulation of myometrial activity during ovine parturition, and that their action may be directed towards the modulation of the frequency of uterine contractions.