Involvement of nitric oxide pathway in prostaglandin F2 α–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 F2α, prostaglandin F2α plus diethylenetriamine–nitric oxide (a donor of nitric oxide), prostaglandin F2α 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 F2α significantly inhibited nitric oxide production by the uterus in a time-dependent manner with maximal effects observed 48 hours after prostaglandin F2α 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 F2α with maximal inhibition at 48 hours after prostaglandin F2α injection. The serum progesterone concentration was substantially reduced by prostaglandin F2α, and this reduction was partially reversed by administration of diethylenetriamine–nitric oxide but not diethylenetriamine without nitric oxide. Prostaglandin F2α caused increases in contractile activity of the uterus in a dose-dependent manner. Diethylenetriamine–nitric oxide (10–4 mol/L) blocked prostaglandin F2α–induced contractions. Premature parturition was induced within 48 hours after prostaglandin F2α injection in 100% of the animals. Coadministration of diethylenetriamine–nitric oxide completely prevented the preterm labor induced by prostaglandin F2α. CONCLUSION: Prostaglandin F2α inhibited inducible nitric oxide synthase messenger ribonucleic acid and subsequent nitric oxide generation in the rat uterus. Nitric oxide can prevent prostaglandin F2α–induced preterm labor, possibly by attenuating the fall in serum progesterone and blocking uterine contractions induced by prostaglandin F2α administration. (Am J Obstet Gynecol 1997;177:907-17)