Buhimschi I A, Shi S Q, Saade G R, Garfield R E
Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Texas Medical Branch, 77555-1062, USA.
Am J Obstet Gynecol. 2001 Mar;184(4):686-93. doi: 10.1067/mob.2001.110448.
Some but not all studies have shown that long-term nitric oxide synthase inhibition during pregnancy induces symptoms similar to those of preeclampsia that include hypertension, proteinuria, and intrauterine growth restriction. This study was undertaken to compare the effects of long-term nitric oxide synthase inhibition during pregnancy on blood pressure and fetal weight between Sprague-Dawley rats from outbred colonies of two different suppliers.
Osmotic minipumps were inserted on day 10 or day 17 of pregnancy in Sprague-Dawley rats obtained from Charles River Laboratories, Inc, Wilmington, Mass, or Harlan Sprague Dawley, Inc, Indianapolis, Ind. The pumps were set to deliver vehicle only (control group) or N omega-nitro-L -arginine methyl ester (a nitric oxide synthase inhibitor) at a rate of 50 mg/d until postpartum day 7. Systolic blood pressures were measured daily with the tail-cuff method. Neonatal weights and survival were recorded.
N omega-nitro-L -arginine methyl ester infusion initiated on gestational day 10 increased blood pressure relative to control levels in all rats studied. Harlan rats were much more sensitive to the hypertensive effect of N omega-nitro-L -arginine methyl ester. When N omega-nitro-L -arginine methyl ester infusion was initiated on gestational day 17, blood pressure increased only in Harlan rats. Pups born to Harlan rats treated with N omega-nitro-L -arginine methyl ester had lower birth weights and a higher stillbirth rate than did pups of Charles River rats. The degree of hypertension was significantly correlated with the deleterious effects of N omega-nitro-L -arginine methyl ester on the fetuses.
Within the same strain of rats the effects of long-term nitric oxide synthase inhibition on blood pressure and fetal outcome depended on the original animal colony, with animals from Harlan Sprague Dawley being more sensitive than those from Charles River Laboratories. This difference in response between animals from different suppliers is most likely caused by genetic differences inbred into the strain. In addition to explaining some of the reported inconsistencies between laboratories, these results may also provide insights into the genetic basis of preeclampsia.
部分但并非所有研究表明，孕期长期抑制一氧化氮合酶会引发类似于先兆子痫的症状，包括高血压、蛋白尿和宫内生长受限。本研究旨在比较孕期长期抑制一氧化氮合酶对来自两家不同供应商远交群的斯普拉格-道利大鼠血压和胎儿体重的影响。
在妊娠第10天或第17天，将渗透微型泵植入从马萨诸塞州威尔明顿的查尔斯河实验室公司或印第安纳州印第安纳波利斯的哈兰·斯普拉格·道利公司获得的斯普拉格-道利大鼠体内。将泵设置为仅输送载体（对照组）或按50毫克/天的速率输送Nω-硝基-L-精氨酸甲酯（一种一氧化氮合酶抑制剂），直至产后第7天。每天用尾套法测量收缩压。记录新生大鼠的体重和存活率。
在妊娠第10天开始输注Nω-硝基-L-精氨酸甲酯，相对于所有研究大鼠的对照水平，血压均升高。哈兰大鼠对Nω-硝基-L-精氨酸甲酯的高血压作用更为敏感。当在妊娠第17天开始输注Nω-硝基-L-精氨酸甲酯时，仅哈兰大鼠的血压升高。用Nω-硝基-L-精氨酸甲酯处理的哈兰大鼠所生幼崽的出生体重低于查尔斯河大鼠所生幼崽，死产率更高。高血压程度与Nω-硝基-L-精氨酸甲酯对胎儿的有害影响显著相关。
在同一品系的大鼠中，长期抑制一氧化氮合酶对血压和胎儿结局的影响取决于原始动物群体，哈兰·斯普拉格·道利公司的动物比查尔斯河实验室的动物更敏感。不同供应商的动物之间这种反应差异很可能是由品系中引入的基因差异引起的。除了解释一些实验室报告的不一致之处外，这些结果还可能为子痫前期的遗传基础提供见解。
