Preterm birth in rats produced by the synergistic action of a nitric oxide inhibitor (NG-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 NG-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 NG-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) NG-nitro-D-arginine methyl ester (50 mg per day) had no effect. (3) inhibition of nitric oxide by NG-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.

• Authors: C Yallampalli, I Buhimschi, K Chwalisz, R E Garfield, Y L Dong
• Journal: American journal of obstetrics and gynecology (Am J Obstet Gynecol) Vol. 175 Issue 1 Pg. 207-12 (Jul 1996) ISSN: 0002-9378 [Print] United States
• PMID: 8694053 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Gonanes
• Hormone Antagonists
• Arginine
• Nitric Oxide Synthase
• onapristone
• NG-Nitroarginine Methyl Ester

Topics

• Animals
• Arginine (administration & dosage, analogs & derivatives, pharmacology)
• Drug Synergism
• Female
• Gonanes (administration & dosage, pharmacology)
• Hormone Antagonists (administration & dosage, pharmacology)
• Infusion Pumps, Implantable
• Injections, Subcutaneous
• NG-Nitroarginine Methyl Ester
• Nitric Oxide Synthase (administration & dosage, antagonists & inhibitors)
• Obstetric Labor, Premature (chemically induced)
• Pregnancy
• Rats
• Rats, Sprague-Dawley
• Time Factors