In vivo administration of nimesulide, a selective PGHS-2 inhibitor, increases in vitro myometrial sensitivity to prostaglandins while lowering sensitivity to oxytocin.
J Soc Gynecol Investig
; 5(6): 296-9, 1998.
Article
en En
| MEDLINE
| ID: mdl-9824808
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. 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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Sulfonamidas
/
Oxitocina
/
Prostaglandinas
/
Inhibidores de la Ciclooxigenasa
/
Miometrio
Tipo de estudio:
Diagnostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Soc Gynecol Investig
Asunto de la revista:
GINECOLOGIA
Año:
1998
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos