The effect of indomethacin on uterine contractility and luteal regression in pregnant rats at term

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Abstract
Treatment of pregnant rats with 1 mg indomethacin/kg twice daily i.m. beginning on day 20 delayed the onset of parturition by about 21 h and prolonged the duration of spontaneous parturition by 4 h. Plasma progesterone and estradiol levels were determined in daily samples of peripheral blood, and uterine contractions were recorded before and during parturition by means of small, chronically implanted intrauterine balloons which were connected to pressure transducers via fluid-filled catheters. Indomethacin treatment did not inhibit or suppress spontaneous or oxytocin-induced contractions, which were of the same intensity in indomethacin-treated as in control rats. Parturition was induced with oxytocin in the same proportion of treated and control rats, but its induction was not successful in treated rats until 1 day later than in controls. The onset of parturition was always related to the plasma progesterone level, which declined at a slower rate in indomethacin-treated than in control rats, reaching baseline values approximately 1 day later in the treated animals. The appearance of 20.alpha.-hydroxysteroid dehydrogenase in the CL [corpoa lutea] of pregnant rats normally occurs on day 21 of gestation, but activity was not observed until about 1 (0-3) day later in the indomethacin-treated rats, indicating that luteolysis was retarded. Prostaglandin F-2.alpha. infusions given on day 21 reversed the effects of indomethacin treatment on plasma progesterone, luteal 20.alpha.-hydroxysteroid dehydrogenase activity and the timing and duration of parturition, and reduced the high perinatal mortality associated with indomethacin treatment, suggesting that the effects of indomethacin were related to its inhibitory action on prostaglandin synthetase activity. In rats, indomethacin may exert its effects on parturition through inhibition of luteal regression which was significantly retarded but not prevented, and that indomethacin does not have a direct effect on myometrial contractility.

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