INVOLVEMENT OF NITRIC-OXIDE PATHWAY IN PROSTAGLANDIN F-2-ALPHA-INDUCED PRETERM LABOR IN RATS

OBJECTIVE: Our purpose was to investigate the roles of nitric oxide an d prostaglandins in controlling parturition. STUDY DESIGN: Pregnant ra ts on day 18 of gestation were injected intraperitoneally with prostag landin F-2 alpha, prostaglandin F-2 alpha, plus diethylenetriamine-nit ric oxide (a donor of nitric oxide), prostaglandin F-2 alpha plus diet hylenetriamine without nitric oxide, or vehicle. Uterine nitrite produ ction, nitric oxide synthase messenger ribonucleic acid and contractil e response in vitro, and serum progesterone levels were measured. The labor and delivery of the rats also were monitored. RESULTS: Exogenous ly administered prostaglandin F-2 alpha significantly inhibited nitric oxide production by the uterus in a time-dependent manner with maxima l effects observed 48 hours after prostaglandin F-2 alpha treatment. M essenger ribonucleic acid for inducible nitric oxide synthase but not endothelial nitric oxide synthase messenger ribonucleic acid in the ut erus was significantly inhibited by prostaglandin F,, with maximal inh ibition at 48 hours after prostaglandin F-2 alpha injection. The serum progesterone concentration was substantially reduced by prostaglandin F-2 alpha, and this reduction was partially reversed by administratio n of diethylenetriamine-nitric oxide but not diethylenetriamine withou t nitric oxide. Prostaglandin F-2 alpha caused increases in contractil e activity of the uterus in a dose-dependent manner. Diethylenetriamin e-nitric oxide (10(-4) mol/L) blocked prostaglandin F-2 alpha-induced contractions. Premature parturition was induced within 48 hours after prostaglandin F-2 alpha injection in 100% of the animals. Coadministra tion of diethylenetriamine-nitric oxide completely prevented the prete rm labor induced by prostaglandin F-2 alpha. CONCLUSION: Prostaglandin F-2 alpha inhibited inducible nitric oxide synthase messenger ribonuc leic acid and subsequent nitric oxide generation in the rat uterus. Ni tric oxide can prevent prostaglandin F-2 alpha-induced preterm labor, possibly by attenuating the fall in serum progesterone and blocking ut erine contractions induced by prostaglandin F-2 alpha administration.