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 and prostaglandins in controlling parturition. STUDY DESIGN: Pregnant rats on day 18 of gestation were injected intraperitoneally with prostaglandin F-2 alpha, prostaglandin F-2 alpha, plus diethylenetriamine-nitric oxide (a donor of nitric oxide), prostaglandin F-2 alpha plus diethylenetriamine without nitric oxide, or vehicle. Uterine nitrite production, nitric oxide synthase messenger ribonucleic acid and contractile response in vitro, and serum progesterone levels were measured. The labor and delivery of the rats also were monitored. RESULTS: Exogenously administered prostaglandin F-2 alpha significantly inhibited nitric oxide production by the uterus in a time-dependent manner with maximal effects observed 48 hours after prostaglandin F-2 alpha treatment. Messenger ribonucleic acid for inducible nitric oxide synthase but not endothelial nitric oxide synthase messenger ribonucleic acid in the uterus was significantly inhibited by prostaglandin F,, with maximal inhibition 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 administration of diethylenetriamine-nitric oxide but not diethylenetriamine without nitric oxide. Prostaglandin F-2 alpha caused increases in contractile activity of the uterus in a dose-dependent manner. Diethylenetriamine-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. Coadministration of diethylenetriamine-nitric oxide completely prevented the preterm labor induced by prostaglandin F-2 alpha. CONCLUSION: Prostaglandin F-2 alpha inhibited inducible nitric oxide synthase messenger ribonucleic acid and subsequent nitric oxide generation in the rat uterus. Nitric oxide can prevent prostaglandin F-2 alpha-induced preterm labor, possibly by attenuating the fall in serum progesterone and blocking uterine contractions induced by prostaglandin F-2 alpha administration.