Yallampalli C, Buhimschi I, Chwalisz K, Garfield R E, Dong Y L
Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston 77555-1062, USA.
Am J Obstet Gynecol. 1996 Jul;175(1):207-12. doi: 10.1016/s0002-9378(96)70276-4.
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.
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.
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.
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.
本研究旨在确定一氧化氮合成的抑制是否会影响抗孕激素引发早产的作用。
从妊娠第16天开始，对孕鼠持续输注NG-硝基-L-精氨酸甲酯。在妊娠第17天，给动物组皮下注射单剂量3或30mg/kg的孕三烯酮；对动物进行长达48小时的早产和分娩监测。
重要发现包括以下结果。（1）NG-硝基-L-精氨酸甲酯（每天50mg）与低剂量孕三烯酮（3mg/kg）联合治疗可导致早产，>70%的胎儿在治疗后27小时内分娩，而单独接受这两种化合物之一的动物中<5%的胎儿分娩。（2）NG-硝基-D-精氨酸甲酯（每天50mg）无作用。（3）NG-硝基-L-精氨酸甲酯对一氧化氮的抑制也显著提高了高剂量孕三烯酮（30mg/kg）在早产和分娩方面的疗效。
用一氧化氮抑制剂与孕三烯酮联合治疗孕鼠可显著增强抗孕激素诱导早产的能力。一氧化氮与孕酮之间的相互作用可能是维持妊娠所必需的。
