title: In vivo administration of nimesulide, a selective PGHS-2 inhibitor, increases in vitro myometrial sensitivity to prostaglandins while lowering sensitivity to oxytocin.
abstract: 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), PGE2 alpha, and oxytocin.
  
  
  METHODS
  Sixteen ovariectomized ewes were infused intravenously with either estradiol (2 micrograms 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 PGE2 alpha, 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 PGE2 alpha and lower in response to oxytocin.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Physiology, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
authors.forename: M
authors.initials: M
authors.lastname: Baguma-Nibasheka
authors.forename: P W
authors.initials: PW
authors.lastname: Nathanielsz
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015237:Dinoprost / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D007527:Isoenzymes / Q000378:metabolism; D009215:Myometrium / Q000187:drug effects*; D010052:Ovariectomy; D010121:Oxytocin / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000494:pharmacology*; D012756:Sheep; D013449:Sulfonamides / Q000494:pharmacology*; D014590:Uterine Contraction / Q000187:drug effects
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D011453:Prostaglandins; D013449:Sulfonamides; D004958:Estradiol; D010121:Oxytocin; D015237:Dinoprost; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; C012655:nimesulide