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Eur J Pharmacol. 2006 Mar 18;534(1-3):218-26. Epub 2006 Feb 21.

Prostaglandins modulate nitric oxide synthase activity early in time in the uterus of estrogenized rat challenged with lipopolysaccharide.

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  • 1Laboratory of Physiopathology of Pregnancy and Labor, Center for Pharmacological and Botanical Studies, CONICET, School of Medicine, University of Buenos Aires, Paraguay 2155, 16th floor, ZIP code C1121ABG, Buenos Aires, Argentina.

Abstract

The aim of our study was to investigate if the lipopolysaccharide (LPS) differentially modulates throughout time the nitric oxide synthase (NOS) and cyclooxygenase (COX) enzymes in the estrogenized rat uterus. To study the effect of LPS throughout time on nitric oxide and prostaglandins production and on NOS and COX expression in the estrogenized rat uterus, females received 5 mg/kg intraperitoneally (i.p.) of LPS and were sacrificed 0.5, 1, 2, 3, 4 and 5 h post-administration. NO production was measured by arginine-citrulline conversion assay and prostaglandin E2/prostaglandin F2alpha by radioconversion. Enzyme expression was evaluated by Western blot analysis. The present work shows that LPS augmented NOS activity 3 h post-treatment and iNOS expression earlier, 2 h post-administration. On the other hand, the administration of LPS stimulated the production of prostaglandin E2/prostaglandin F2alpha and augmented the expression of COX-I 1 h after the treatment and of COX-II 2 h post-treatment. Meloxicam, a COX-II inhibitor, stimulated NO production in a group of rats injected i.p. with both LPS and the inhibitor and sacrificed 2 h after the treatment. These results indicate that, in the estrogenized rat uterus challenged with LPS, the early stimulation in the production of prostaglandins inhibited NOS activity, until the expression of the NOS isoforms is sufficient to overpass the inhibitory effect of the prostaglandins. The above findings suggest that the interaction between NOS and COX might be important in the regulation of physiopathologic events during pregnancy.

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