Effects of aminoguanidine and cyclooxygenase inhibitors on nitric oxide and prostaglandin production, and nitric oxide synthase and cyclooxygenase expression induced by lipopolysaccharide in the estrogenized rat uterus.
OBJECTIVE
The aim of our study was first to investigate if there exists an interaction between nitric oxide (NO) and prostaglandin (PG) generation in the estrogenized rat uterus challenged by lipopolysaccharide (LPS), and, secondly, which isoforms of nitric oxide synthase (NOS) and cyclooxygenase (COX) participate in this process.


METHODS
To study the effect of LPS and to characterize the isoenzymes involved in the process, specific inhibitors of iNOS (aminoguanidine) and COX-II (meloxicam, nimesulide) and non-specific of COX (indomethacin) were injected intraperitoneally to determine their effect on NO and PG production, and on NOS and COX expression induced by LPS in estrogenized rat uterus. NO production was measured by arginine-citrulline conversion assay and PGE(2)/PGF(2alpha,)by radioconversion. Enzyme expression was evaluated by Western blot analysis.


RESULTS
The present work shows that iNOS inhibitor, aminoguanidine, reduced NO and PGE(2)/PGF(2alpha) production induced by LPS injection. Aminoguanidine exerts its effect over the PG metabolism by inhibiting COX-II activity and expression. On the other hand, both indomethacin, a non-selective PG inhibitor, and meloxicam, a COX-II inhibitor, stimulated NO production and reduced PGE(2)/PGF(2alpha) generation. Indomethacin also reduced COX-II and iNOS expression.


CONCLUSIONS
These results indicate that in the estrogenized rat uterus challenged with LPS, PG and NO interact affecting each other's metabolic pathways. The above findings indicate that the interaction between NOS and COX might be important in the regulation of physiopathologic events during pregnancy.
Ribeiro
María
M
Laboratorio de Fisio-patología de la Preñez y el Parto, Centro de Estudios Farmacológicos y Botánicos (CEFYBO, CONICET), Buenos Aires, Argentina. marialribeiro@yahoo.com.ar
Cella
Maximiliano
M
Farina
Mariana
M
Franchi
Ana
A
D000818:Animals; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015237:Dinoprost / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D020964:Embryo Loss / Q000201:enzymology / Q000503:physiopathology; D004967:Estrogens / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D006146:Guanidines / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000201:enzymology / Q000503:physiopathology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008070:Lipopolysaccharides; D000077239:Meloxicam; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D011247:Pregnancy; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology; D013843:Thiazines / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D014599:Uterus / Q000187:drug effects* / Q000201:enzymology* / Q000503:physiopathology
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D004967:Estrogens; D006146:Guanidines; D007527:Isoenzymes; D008070:Lipopolysaccharides; D011453:Prostaglandins; D013449:Sulfonamides; D013843:Thiazines; D013844:Thiazoles; D009569:Nitric Oxide; D015237:Dinoprost; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; C004479:pimagedine; C012655:nimesulide; D000077239:Meloxicam; D007213:Indomethacin