Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39206, USA.
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39206, USA.
Pregnancy Hypertens. 2021 Jun;24:50-57. doi: 10.1016/j.preghy.2021.02.009. Epub 2021 Feb 23.
Preeclampsia affects 5-8% of pregnancies and is characterized by hypertension, placental ischemia, neurological impairment, and an increase in circulating inflammatory cytokines, including Interleukin-17 (IL17). While placental ischemia has also been shown to impair cerebrovascular function, it is not known which placental-associated factor(s) drive this effect. The purpose of this study was to examine the effects of IL17 on cerebrovascular function during pregnancy. To achieve this goal, pregnant rats were infused with either IL17 (150 pg/day, 5 days, osmotic minipump), or vehicle (saline/0.7% BSA osmotic minipump) starting at gestational day (GD) 14. On GD 19, the cerebral blood flow (CBF) response to increases in mean arterial pressure (MAP) was measured in vivo, and myogenic constrictor responses of the middle cerebral artery (MCA) were assessed ex vivo. IL17 increased MAP but impaired CBF responses only at the highest arterial pressure measured (190 mmHg). Myogenic constrictor responses overall were mostly unaffected by IL17 infusion; however, the intraluminal pressure at which peak myogenic tone was generated was lower in the IL17 infused group (120 vs 165 mm Hg), suggesting maximal tone is exerted at lower intraluminal pressures in IL17-treated pregnant rats. Consistent with the lack of substantial change in overall myogenic responsiveness, there was no difference in cerebral vessel expression of putative mechanosensitive protein βENaC, but a tendency towards a decrease in ASIC2 (p = 0.067) in IL17 rats. This study suggests that infusion of IL17 independent of other placental ischemia-associated factors is insufficient to recapitulate the features of impaired cerebrovascular function during placental ischemia. Further studies to examine of the role of other pro-inflammatory cytokines, individually or a combination, are necessary to determine mechanisms of cerebral vascular dysfunction during preeclampsia.
子痫前期影响 5-8%的妊娠，其特征是高血压、胎盘缺血、神经损伤以及循环中炎症细胞因子的增加，包括白细胞介素 17（IL17）。虽然胎盘缺血也已被证明会损害脑血管功能，但尚不清楚哪些胎盘相关因素导致了这种影响。本研究旨在检查 IL17 在妊娠期间对脑血管功能的影响。为了实现这一目标，从妊娠第 14 天开始，给怀孕大鼠输注 IL17（150pg/天，5 天，渗透微型泵）或载体（盐水/0.7%BSA 渗透微型泵）。在妊娠第 19 天，通过体内测量平均动脉压（MAP）升高时的脑血流（CBF）反应，以及评估体外大脑中动脉（MCA）的肌源性收缩反应来评估。IL17 增加了 MAP，但仅在测量的最高动脉压（190mmHg）时才损害了 CBF 反应。IL17 输注对肌源性收缩反应的总体影响不大；然而，在 IL17 输注组中产生最大肌源性张力的管腔内压力较低（120 与 165mmHg），这表明在 IL17 处理的怀孕大鼠中，最大张力在较低的管腔内压力下发挥作用。与整体肌源性反应没有明显变化一致，IL17 大鼠中潜在的机械敏感蛋白βENaC 的脑血管表达没有差异，但 ASIC2 的趋势下降（p=0.067）。这项研究表明，输注 IL17 而不考虑其他与胎盘缺血相关的因素，不足以重现胎盘缺血期间脑血管功能受损的特征。需要进一步研究来检查其他促炎细胞因子单独或联合的作用，以确定子痫前期期间脑血管功能障碍的机制。
