BACKGROUND Placental ischemia and hypertension, characteristic features of preeclampsia, are associated with impaired cerebral blood flow (CBF) autoregulation and cerebral edema. However, the factors that contribute to these cerebral abnormalities are not clear. Several lines of evidence suggest that angiotensin II can impact cerebrovascular function; however, the role of the renin angiotensin system in cerebrovascular function during placental ischemia has not been examined. We tested whether the angiotensin type 1 (AT1) receptor contributes to impaired CBF autoregulation in pregnant rats with placental ischemia caused by surgically reducing uterine perfusion pressure. METHODS Placental ischemic or sham operated rats were treated with vehicle or losartan from gestational day (GD) 14 to 19 in the drinking water. On GD 19, we assessed CBF autoregulation in anesthetized rats using laser Doppler flowmetry. RESULTS Placental ischemic rats had impaired CBF autoregulation that was attenuated by treatment with losartan. In addition, we examined whether an agonistic autoantibody to the AT1 receptor (AT1-AA), reported to be present in preeclamptic women, contributes to impaired CBF autoregulation. Purified rat AT1-AA or vehicle was infused into pregnant rats from GD 12 to 19 via mini-osmotic pumps after which CBF autoregulation was assessed. AT1-AA infusion impaired CBF autoregulation but did not affect brain water content. CONCLUSIONS These results suggest that the impaired CBF autoregulation associated with placental ischemia is due, at least in part, to activation of the AT1 receptor and that the RAS may interact with other placental factors to promote cerebrovascular changes common to preeclampsia.

中文翻译：

---

血管紧张素 II I 型受体会导致妊娠大鼠胎盘缺血引起的脑血流自动调节受损。


背景胎盘缺血和高血压是先兆子痫的特征，与脑血流（CBF）自动调节受损和脑水肿有关。然而，导致这些大脑异常的因素尚不清楚。多项证据表明血管紧张素 II 可以影响脑血管功能；然而，肾素血管紧张素系统在胎盘缺血期间脑血管功能中的作用尚未得到研究。我们测试了 1 型血管紧张素 (AT1) 受体是否会导致因手术降低子宫灌注压而导致胎盘缺血的妊娠大鼠 CBF 自动调节受损。方法 胎盘缺血或假手术大鼠从妊娠第 14 至 19 天开始用赋形剂或氯沙坦加饮用水治疗。在 GD 19 上，我们使用激光多普勒血流计评估了麻醉大鼠的 CBF 自动调节。结果 胎盘缺血大鼠的 CBF 自动调节功能受损，氯沙坦治疗可减弱这种功能。此外，我们还检查了据报道先兆子痫女性中存在的 AT1 受体激动性自身抗体 (AT1-AA) 是否会导致 CBF 自身调节受损。将纯化的大鼠 AT1-AA 或载体通过微型渗透泵注入 GD 12 至 19 岁的怀孕大鼠中，然后评估 CBF 自动调节。 AT1-AA输注会损害CBF自动调节，但不影响脑含水量。结论 这些结果表明，与胎盘缺血相关的 CBF 自身调节受损至少部分是由于 AT1 受体的激活，并且 RAS 可能与其他胎盘因子相互作用，促进先兆子痫常见的脑血管变化。