Buhimschi I, Yallampalli C, Chwalisz K, Garfield R E
University of Texas Medical Branch, Department of Obstetrics and Gynecology, Galveston, USA.
Hum Reprod. 1995 Oct;10(10):2723-30. doi: 10.1093/oxfordjournals.humrep.a135775.
The aim of this study was to establish that inhibiting nitric oxide (NO) production with NG-nitro-L-arginine methyl ester (L-NAME) results in high blood pressure conditions in chronically treated pregnant rats. To validate the model, the effects of L-arginine (the substrate for NO) and D-arginine (the stereoisomer of L-arginine which is not a substrate for NO synthesis) were studied on blood pressure and fetal weights. The effects of a progesterone agonist, promegestone (R5020) and 17 beta-oestradiol were also explored. The NO synthase inhibitor L-NAME was chronically infused s.c. into pregnant rats from day 17 of gestation, either alone or with the simultaneous infusion of L-arginine and injections of sex steroid hormones (promegestone and oestradiol), compounds that may act in the pathogenic pathways of pre-eclampsia. Systolic blood pressure was measured daily. Weight and mortality of pups were recorded immediately after delivery. Blood pressure was elevated significantly in rats treated with L-NAME for only 1 day following infusion; there was a consistent decline during the next 3 days of pregnancy followed by a dramatic and significant rise just prior to delivery and post-partum. Fetal weights were reduced significantly in the L-NAME-treated rats. Co-treatment of L-NAME-infused rats with L-arginine reversed both the increase in blood pressure and the decrease in fetal weights observed with L-NAME alone. R5020, but not oestradiol, also reduced blood pressure and increased fetal weights in the L-NAME-treated animals. NO appears to play essential roles in the regulation of blood pressure during pregnancy, as well as in fetal perfusion and fetal weights at delivery. This study also indicates that progesterone, and not oestrogen, may regulate the vascular adaptations during normal pregnancy. L-Arginine and progesterone agonists like promegestone may have beneficial effects on the high blood pressure levels and reduced fetal weights associated with pre-eclampsia.
本研究的目的是确定用NG-硝基-L-精氨酸甲酯（L-NAME）抑制一氧化氮（NO）生成会导致长期治疗的妊娠大鼠出现高血压情况。为验证该模型，研究了L-精氨酸（NO的底物）和D-精氨酸（L-精氨酸的立体异构体，不是NO合成的底物）对血压和胎儿体重的影响。还探究了孕激素激动剂普罗美孕酮（R5020）和17β-雌二醇的作用。从妊娠第17天起，将NO合酶抑制剂L-NAME皮下长期注入妊娠大鼠体内，单独注入或同时注入L-精氨酸以及注射可能在子痫前期致病途径中起作用的性类固醇激素（普罗美孕酮和雌二醇）。每天测量收缩压。分娩后立即记录幼崽的体重和死亡率。注入L-NAME仅1天后，大鼠血压显著升高；在接下来的3天孕期中血压持续下降，随后在分娩前和产后急剧显著上升。L-NAME处理的大鼠胎儿体重显著降低。用L-精氨酸对注入L-NAME的大鼠进行联合治疗可逆转单独使用L-NAME时观察到的血压升高和胎儿体重降低。R5020而非雌二醇也降低了L-NAME处理动物的血压并增加了胎儿体重。NO似乎在妊娠期间血压调节以及分娩时胎儿灌注和胎儿体重方面发挥着重要作用。本研究还表明，在正常妊娠期间，是孕激素而非雌激素可能调节血管适应性。L-精氨酸和像普罗美孕酮这样的孕激素激动剂可能对与子痫前期相关的高血压水平和降低的胎儿体重具有有益作用。
