OBJECTIVE: To investigate the action of prostaglandin synthesis inhibitors on uterine sensitivity to established stimulants of myometrial activity, we tested the effect of in vivo administration of nimesulide, a selective cyclooxygenase-2 inhibitor, into ovariectomized nonpregnant sheep on subsequent in vitro myometrial responsiveness to prostaglandin E2 (PGE2), PGE2α, and oxytocin. METHODS: Sixteen ovariectomized ewes were infused intravenously with either estradiol (2 μg h, n = 8) or estradiol plus nimesulide (20 mg h, n = 8); for 48 h before necropsy. Longitudinal strips of myometrium were superfused with Krebs buffer solution and their spontaneous baseline contractility recorded after 1 hour. pD2 values and maximum percentage increases in contractile tension were derived from dose- response curves to 10-9 to 10-5 mol/L PGE2 and PGE2α, and 10-11 to 10-7 mol/L oxytocin. RESULTS: Baseline activity was lower in myometrium from estradiol-treated ewes infused with nimesulide as compared with ewes infused with estradiol alone. Maximum tension increase in response to all three agonists was similar in myometrium from estradiol- and nimesulide- treated ewes, but the pD2 in myometrium from nimesulide-treated ewes was higher in response to PGE2 and PGE2α and lower in response to oxytocin. CONCLUSION: The results show that nimesulide lowers spontaneous myometrial contractility and sensitivity to oxytocin while increasing sensitivity to PGs, indicating a down-regulation of oxytocin receptor and an up-regulation of PG receptors and/or intracellular signaling events.
|Original language||English (US)|
|Number of pages||4|
|Journal||Journal of the Society for Gynecologic Investigation|
|State||Published - Nov 1998|
ASJC Scopus subject areas
- Obstetrics and Gynecology