Preterm birth in rats produced by the synergistic action of a nitric oxide inhibitor (N G-nitro-L-arginine methyl ester) and an antiprogestin (onapristone)

Abstract

OBJECTIVE: The aim of this study was to determine whether inhibition of nitric oxide synthesis would affect the action of an antiprogesterone to provoke preterm labor. STUDY DESIGN: Pregnant rats were continuously infused with N G-nitro- L-arginine methyl ester starting on day 16 of gestation. On day 17 of gestation groups of animals were injected subcutaneously with a single dose of either 3 or 30 mg/kg onapristone; animals were monitored for preterm labor and delivery for up to 48 hours. RESULTS: Significant findings included the following results. (1) Combined treatment with N G-nitro- L-arginine methyl ester (50 mg per day) and low-dose onapristone (3 mg/kg) produced preterm labor; >70% of the fetuses were delivered within 27 hours of treatment, whereas <5% of the fetuses were delivered in the animals receiving either of these compounds alone. (2) N G-nitro- D-arginine methyl ester (50 mg per day) had no effect. (3) Inhibition of nitric oxide by N G-nitro- L-arginine methyl ester also significantly increased the efficacy of high-dose onapristone (30 mg/kg) in preterm labor and delivery. CONCLUSION: Treatment of pregnant rats with a combination of a nitric oxide inhibitor with onapristone significantly potentiated the ability of the antiprogesterone to induce preterm labor. The interaction of nitric oxide and progesterone may be required to maintain pregnancy. (Am J Obstet Gynecol 1996;175:207-12.)