Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Vermont College of Medicine, Burlington, VT, USA.
Hypertension. 2010 Nov;56(5):1003-8. doi: 10.1161/HYPERTENSIONAHA.110.158931. Epub 2010 Sep 20.
Circulating factors in preeclamptic women are thought to cause endothelial dysfunction and thereby contribute to the progression of this hypertensive condition. Despite the involvement of neurological complications in preeclampsia, there is a paucity of data regarding the effect of circulating factors on cerebrovascular function. Using a rat model of pregnancy, we investigated blood-brain barrier permeability, myogenic activity, and the influence of endothelial vasodilator mechanisms in cerebral vessels exposed intraluminally to plasma from normal pregnant or preeclamptic women. In addition, the role of vascular endothelial growth factor signaling in mediating changes in permeability in response to plasma was investigated. A 3-hour exposure to 20% normal pregnant or preeclamptic plasma increased blood-brain barrier permeability by ≈6.5- and 18.0-fold, respectively, compared with no plasma exposure (P<0.01). Inhibition of vascular endothelial growth factor receptor kinase activity prevented the increase in permeability in response to preeclamptic plasma but had no effect on changes in permeability of vessels exposed to normal pregnant plasma. Circulating factors in preeclamptic plasma did not affect myogenic activity or the influence of endothelium on vascular tone. These findings demonstrate that acute exposure to preeclamptic plasma has little effect on reactivity of cerebral arteries but significantly increases blood-brain barrier permeability. Prevention of increased permeability by inhibition of vascular endothelial growth factor signaling suggests that activation of this pathway may be responsible for increased blood-brain barrier permeability after exposure to preeclamptic plasma.
先兆子痫妇女的循环因子被认为会导致内皮功能障碍，并因此促进这种高血压状况的发展。尽管先兆子痫涉及神经并发症，但关于循环因子对脑血管功能的影响的数据很少。我们使用妊娠大鼠模型，研究了暴露于正常妊娠或先兆子痫妇女血浆内的脑血管的血脑屏障通透性、肌源性活性以及内皮血管舒张机制的影响。此外，还研究了血管内皮生长因子信号转导在介导对血浆的通透性变化中的作用。与无血浆暴露相比，暴露于 20%的正常妊娠或先兆子痫血浆 3 小时可分别使血脑屏障通透性增加约 6.5 倍和 18.0 倍（P<0.01）。抑制血管内皮生长因子受体激酶活性可防止对先兆子痫血浆的通透性增加，但对暴露于正常妊娠血浆的血管的通透性变化无影响。先兆子痫妇女的循环因子既不影响肌源性活性，也不影响内皮对血管张力的影响。这些发现表明，急性暴露于先兆子痫血浆对大脑动脉的反应性几乎没有影响，但显著增加了血脑屏障的通透性。通过抑制血管内皮生长因子信号转导来预防通透性增加表明，该途径的激活可能是暴露于先兆子痫血浆后血脑屏障通透性增加的原因。
