INHIBITION OF PROSTAGLANDIN PRODUCTION BY NIMESULIDE IS ACCOMPANIED BY CHANGES IN EXPRESSION OF THE CASSETTE OF UTERINE LABOR-RELATED GENESIN PREGNANT SHEEP

The present study was designed to characterize effects of inhibiting P G production by infusing nimesulide (CAS 51803-78-2) on PGE(2) product ion and expression of uterine labor-related genes in pregnant sheep. M yometrium, endometrium, and placenta were collected following 6 h of i v nimesulide or vehicle infusion. Infusions were commenced 9 h after o nset of spontaneous term labor. Tissues were also collected from term control ewes not in labor. PGE(2) was measured in fetal plasma by RIA. ER, OTR, Hsp 70 and 90, cPLA2, and PGHS-2 messenger RNA (mRNA) abunda nce in myometrium, endometrium, and PGHS-2 in placenta were quantified by Northern blot analysis. Fetal plasma PGE(2) decreased during nimes ulide infusion (P < 0.05). ER, OTR, Hsp 70, and Hsp 90 mRNA increased during spontaneous term labor in vehicle infused ewes in both myometri um and endometrium. In myometrium after nimesulide infusion, OTR and H sp 70 mRNA decreased significantly (P < 0.05) compared with vehicle in fused animals, but the decrease in Hsp 90 and ER mRNA fell outside the level of significance. In the endometrium, nimesulide produced a decr ease in ER and OTR mRNA (P < 0.05) compared with vehicle infused anima ls, but the changes in Hsp 90 and 70 mRNA fell outside the level of si gnificance. Nimesulide reversed the up-regulation of PGHS-2 mRNA that occurred in myometrium, endometrium, and placenta during vehicle infus ion (P < 0.05). cPLA2 was only elevated in the endometrium in vehicle infused ewes and did not change in either endometrium or myometrium af ter nimesulide infusion. Conclusions: Inhibition of PG production resu lted in decreased fetal plasma PGE(2). The decreased abundance of mRNA for several of the well described cassette of utero-placental labor-r elated genes following nimesulide inhibition may result from altered P G production.