Wallace Kedra, Tremble Sarah M, Owens Michelle Y, Morris Rachael, Cipolla Marilyn J
Department of Obstetrics & Gynecology, University of Mississippi Medical Center, Jackson, MS, USA
Department of Neurological Sciences, University of Vermont College of Medicine, Burlington, VT, USA Department of Obstetrics, Gynecology & Reproductive Sciences, University of Vermont College of Medicine, Burlington, VT, USA Department of Pharmacology, University of Vermont College of Medicine, Burlington, VT, USA.
Reprod Sci. 2015 Mar;22(3):278-84. doi: 10.1177/1933719114549844. Epub 2014 Sep 6.
Circulating inflammatory factors and endothelial dysfunction have been proposed to contribute to the pathophysiology of hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. To date, the occurrence of neurological complications in these women has been reported, but few studies have examined whether impairment in blood-brain barrier (BBB) permeability or cerebrovascular reactivity is present in women having HELLP syndrome. We hypothesized that plasma from women with HELLP syndrome causes increased BBB permeability and cerebrovascular dysfunction. Posterior cerebral arteries from female nonpregnant rats were perfused with 20% serum from women with normal pregnancies (n = 5) or women with HELLP syndrome (n = 5), and BBB permeability and vascular reactivity were compared. Plasma from women with HELLP syndrome increased BBB permeability while not changing myogenic tone and reactivity to pressure. Addition of the nitric oxide (NO) synthase inhibitor N(ω)-nitro-L-arginine methyl ester caused constriction of arteries that was not different with the different plasmas nor was dilation to the NO donor sodium nitroprusside different between the 2 groups. However, dilation to the small- and intermediate-conductance, calcium-activated potassium channel activator NS309 was decreased in vessels exposed to HELLP plasma. Thus, increased BBB permeability in response to HELLP plasma was associated with selective endothelial dysfunction.
循环炎症因子和内皮功能障碍被认为与溶血、肝酶升高和血小板减少（HELLP）综合征的病理生理学有关。迄今为止，已有关于这些女性发生神经并发症的报道，但很少有研究探讨患有HELLP综合征的女性是否存在血脑屏障（BBB）通透性受损或脑血管反应性异常。我们假设，HELLP综合征女性的血浆会导致BBB通透性增加和脑血管功能障碍。用正常妊娠女性（n = 5）或HELLP综合征女性（n = 5）的20%血清灌注雌性未孕大鼠的大脑后动脉，并比较BBB通透性和血管反应性。HELLP综合征女性的血浆增加了BBB通透性，同时不改变肌源性张力和对压力的反应性。添加一氧化氮（NO）合酶抑制剂N（ω）-硝基-L-精氨酸甲酯会引起动脉收缩，不同血浆之间无差异，两组对NO供体硝普钠的舒张反应也无差异。然而，暴露于HELLP血浆的血管对小电导和中电导钙激活钾通道激活剂NS309的舒张反应降低。因此，对HELLP血浆的反应中BBB通透性增加与选择性内皮功能障碍有关。
