Interaction between nitric oxide and prostaglandin E pathways in rat smooth muscle myometrial cells

Previously, we demonstrated the presence of a nitric oxide (NO) prostagland in (PG) pathway in myometrial cells obtained from uterine rat tissue. This pathway was modulated by estrogen and one possible function could be to mod ulate uterine relaxation. In the present study, we investigated the role of progesterone in the regul ation of NO synthesis and the uterotonic PGE production by myometrial cells from uterine rat tissue. We worked with two groups of rats: (i) ovariectom ized (OV) rats, without influence of sex hormones and (ii) OV rats injected with progesterone (4 mg) s.c. Myometrial uterine cells were obtained by a selective enzymatic digestion. In the incubation medium of these cells, nit rite concentration (as a measure of NO production) and PGE production were evaluated. To ensure a specific response, a competitive NOs inhibitor, N-G- monomethyl-L-arginine; L-NMMA (300 mu M) was used. We found that at 48 h of the incubation period, cells obtained from progest erone-primed uterine tissue presented an increase in the nitrite concentrat ion concomitant with a decrease in the PGE production. When L-NMMA was adde d to the cells, nitrite production and PGE synthesis returned to control va lues. The fact that this effect had not been observed in the group of cells obtained from OV rats suggests that progesterone was responsible for it. T hese data provide strong evidence that in spite of the fact that estrogen a nd progesterone modulate the NO-PO pathway in the uterine rat tissue, the t wo hormones have opposite effects.