In Vivo Administration of Nimesulide, a Selective PGHS-2 Inhibitor, Increases In Vitro Myometrial Sensitivity to Prostaglandins While Lowering Sensitivity to Oxytocin.

Baguma-Nibasheka, Mark; Nathanielsz, Peter W.

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.

Reproductive Sciences, 1998, Vol 5, Issue 6, p296

1933-7191

Academic Journal

10.1177/107155769800500603