Crosstalk between nitric oxide synthase and cyclooxygenase metabolites in the estrogenized rat uterus

Abstract

In the present study, we investigated the effect of nitric oxide (NO) and prostaglandins (PGs) on the production of arachidonate and l-arginine metabolites. We found that in the estrogenized rat uterus lipopolysaccharide (LPS) 5 mg/kg induced NO and PGs synthesis simultaneously. The uteri were incubated with different doses of an NO donor: NP 300 and 600 μM. The results indicate that both doses of NP produce a significant increase (P<0.01) in all prostanoids evaluated. The stimulatory effect was completely reversed by the addition of 2 μg/ml of hemoglobin (Hb), an NO scavenger. However, NOS inhibitor, N^G-l-monomethyl arginine had no effect on basal prostanoid production. We also studied NO synthesis in the presence of different PGs concentration. We found that PGF_2α and PGD₂ were capable of reversing LPS stimulation on NO synthesis (P<0.05), in all the doses evaluated. On the other hand, PGE₂ 10⁻¹⁰ and 10⁻⁹ M potentated LPS effect (P<0.001). These results suggest that in the estrogenized rat uterus, the synthesis of cyclooxygenase metabolites is positively regulated by NO, while NO synthesis regulation depends on the PGs evaluated.