Sakawi Y, Tarpey M, Chen Y F, Calhoun D A, Connor M G, Chestnut D H, Parks D A
Department of Anesthesiology, University of Alabama at Birmingham, 35233-6810, USA.
Anesthesiology. 2000 Dec;93(6):1446-55. doi: 10.1097/00000542-200012000-00017.
Recent evidence implicates nitric oxide (*NO) in the pathogenesis of preeclampsia. The authors tested the hypothesis that administration of low-dose endotoxin to pregnant rats mimics the signs of preeclampsia in humans and that *NO and *NO-derived species play a role in that animal model.
Endotoxin was infused at doses of 1, 2 and 10 microg/kg over 1 h to rats on day 14 of pregnancy. Mean arterial pressure, urinary protein, urinary and plasma nitrite plus nitrate (NO2- + NO3-) concentrations, and platelet count were measured before and after the endotoxin infusion. In another group of pregnant rats, the nitric oxide synthase inhibitor L-nitroarginine methyl ester (L-NAME) was administered in drinking water at a dose of 3 mg x kg(-1) x d(-1) starting on day 7 of pregnancy. Endotoxin was then infused at 10 microg/kg on day 14 of pregnancy. Kidneys and uteroplacental units were examined histologically and analyzed immunohistochemically for 3-nitrotyrosine.
Endotoxin administration at doses of 2 and 10 microg/kg caused proteinuria and thrombocytopenia in pregnant rats, but did not result in hypertension. Urinary NO2- + NO3- concentration, reflective of tissue *NO production rates, was significantly elevated in pregnant rats that received endotoxin at 10 microg/kg. Ingestion of L-NAME caused hypertension. Tissues from pregnant rats treated with L-NAME, endotoxin at 10 microg/kg, and a combination of L-NAME and endotoxin had increased 3-nitrotyrosine immunoreactivity.
Nitric oxide either directly or through secondary species plays a significant role in the biochemical and physiologic changes that occur in a rodent model of endotoxin-induced injury.
近期证据表明一氧化氮（NO）与子痫前期的发病机制有关。作者检验了以下假设：给妊娠大鼠注射低剂量内毒素可模拟人类子痫前期的症状，且NO及*NO衍生物质在该动物模型中发挥作用。
在妊娠第14天，给大鼠在1小时内分别输注剂量为1、2和10微克/千克的内毒素。在内毒素输注前后测量平均动脉压、尿蛋白、尿及血浆中亚硝酸盐加硝酸盐（NO2- + NO3-）浓度以及血小板计数。在另一组妊娠大鼠中，从妊娠第7天开始，在饮用水中给予一氧化氮合酶抑制剂L-硝基精氨酸甲酯（L-NAME），剂量为3毫克·千克-1·天-1。然后在妊娠第14天给大鼠输注10微克/千克的内毒素。对肾脏和子宫胎盘单位进行组织学检查，并对3-硝基酪氨酸进行免疫组织化学分析。
给予2和10微克/千克剂量的内毒素可导致妊娠大鼠出现蛋白尿和血小板减少，但未引起高血压。反映组织*NO生成率的尿NO2- + NO3-浓度在接受10微克/千克内毒素的妊娠大鼠中显著升高。摄入L-NAME可导致高血压。用L-NAME、10微克/千克内毒素以及L-NAME与内毒素联合处理的妊娠大鼠组织中，3-硝基酪氨酸免疫反应性增加。
一氧化氮直接或通过其衍生物质在啮齿动物内毒素诱导损伤模型中发生的生化和生理变化中起重要作用。
