NITRIC-OXIDE INHIBITION CAUSES INTRAUTERINE GROWTH-RETARDATION AND HINDLIMB DISRUPTIONS IN RATS

NITRIC-OXIDE INHIBITION CAUSES INTRAUTERINE GROWTH-RETARDATION AND HINDLIMB DISRUPTIONS IN RATS
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DOI:
10.1016/0002-9378(94)90141-4
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发表时间:
1994-11-01
影响因子:
9.8
通讯作者:
MILLER, MJS
MILLER, MJS
中科院分区:
医学1区
文献类型:
--
作者:
DIKET, AL;PIERCE, MR;MILLER, MJS

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目的:我们的目的是确定一氧化氮合酶抑制对母亲和胎儿健康的影响,在最后三分之一的pregnancy.Study设计:孕鼠进行了治疗,从妊娠第13天到第19天或第20天的一氧化氮合酶抑制剂N-G-硝基-L-精氨酸甲酯,这是在饮用水随意管理。对照动物接受无活性对映体N-G-硝基-D-精氨酸甲酯或不接受治疗。测定母体血压、血液化学研究、胎盘和幼仔大小。另一组大鼠接受硝普钠与N-G-硝基-L-精氨酸甲酯联合给药。结果:N-G-硝基-L-精氨酸甲酯可剂量依赖性地减少胎盘和幼崽的大小。在0.1 mg/ml剂量下,羊水中环磷酸鸟苷水平显著降低,但在更高剂量下则无此现象。胎仔后肢的出血性坏死仅发生在N-G-硝基-L-精氨酸甲酯治疗时,并可通过同时给予硝普钠进行预防。母亲的血压和血液和尿液化学研究不受影响的N-G-硝基-L-精氨酸methylester.CONCLUSION:慢性减少一氧化氮生产的最后三分之一的妊娠导致显着的宫内发育迟缓和出血性破坏的后肢。产妇并发症是最小的,并没有模仿先兆子痫。
OBJECTIVE: Our purpose was to determine the effects of nitric oxide synthase inhibition on maternal and fetal health in the last third of pregnancy.STUDY DESIGN: Pregnant rats were treated from gestational day 13 to day 19 or 20 with the nitric oxide synthase inhibitor N-G-nitro-L-arginine methyl ester, which was administered in the drinking water ad libitum. Control animals received the inactive enantiomer N-G-nitro-D-arginine methyl ester or no treatment. Maternal blood pressure, blood chemistry studies, and placenta and pup size were determined. A separate group of rats received nitroprusside sodium in conjunction with N-G-nitro-L-arginine methyl ester.RESULTS: N-G-nitro-L-arginine methyl ester caused a dose-dependent reduction in placenta and pup size. Amniotic fluid levels of cyclic guanosine monophosphate were significantly reduced at 0.1 mg/ml but not at higher doses. Hemorrhagic necrosis of fetal hind limbs occurred only with treatment with N-G-nitro-L-arginine methyl ester and was prevented by coadministration of nitroprusside sodium. Maternal blood pressure and blood and urine chemistry studies were unaffected by N-G-nitro-L-arginine methyl ester.CONCLUSION: Chronic reductions of nitric oxide production in the last third of pregnancy result in significant intrauterine growth retardation and hemorrhagic disruptions of hind limbs. Maternal complications were minimal and did not mimic preeclampsia.