Campbell Nathan, Strong Luke, Fang Xing, Border Jane J, Herrock Owen, Turner Ty, Deer Evangeline, Amaral Lorena, Dechend Ralf, Roman Richard J, LaMarca Babbette
Department of Pharmacology & Toxicology, University of Mississippi Medical Center, Jackson, MS, USA.
Charité, Campus Buch, Experimental and Clinical Research Center, HELIOS Clinic, Berlin-Buch, Germany.
Int J Cerebrovasc Dis Stroke. 2023;6(1). doi: 10.29011/2688-8734.100154. Epub 2023 Jul 17.
Preeclampsia (PE), new-onset hypertension during pregnancy alongside organ dysfunction, is a leading cause of morbidity and mortality for the mother and fetus. PE women have activated B cells that produce agonistic autoantibodies to the angiotensin II type 1 receptor (AT1-AA). AT1-AA impairs cerebral blood flow (CBF) autoregulation during pregnancy. Although AT1-AA often remains elevated up to 8 years postpartum, AT1-AA's effect on CBF autoregulation postpartum is unknown. This study examined whether elevated AT1-AA during pregnancy impairs CBF autoregulation postpartum and if this was augmented by infusion of AT1-AA postpartum. AT1-AA was infused into 12-week-old timed-pregnant Sprague Dawley rats beginning on gestational day 14. Uterine artery resistance index (UARI) was measured on gestational day 18 as a measure of endothelial dysfunction associated with PE. Dams were allowed to deliver. One group was given a second infusion of AT1-AA (50% perinatal dose mimicking levels observed in postpartum PE women) at 9 weeks postpartum. After postpartum week 10, mean arterial pressure (MAP) was measured in conscious rats and CBF autoregulation was measured by laser Doppler flowmetry. AT1-AA during pregnancy increased UARI (P<0.05). AT1-AA during pregnancy did not affect MAP postpartum but did impair CBF autoregulation postpartum. Infusion of AT1-AA postpartum significantly elevated blood pressure (P<0.01) but did not further impair CBF autoregulation. This study demonstrates that circulating AT1-AA during pregnancy causes impairment of CBF autoregulation well into the postpartum period indicating that elevated AT1-AA leads to long-term cerebrovascular consequences. Targeting AT1-AA may prevent cerebrovascular effects associated with PE during pregnancy and postpartum.
子痫前期（PE）是指孕期出现的新发高血压并伴有器官功能障碍，是导致母婴发病和死亡的主要原因。患有PE的女性体内B细胞被激活，产生针对1型血管紧张素II受体的激动性自身抗体（AT1-AA）。AT1-AA会损害孕期的脑血流（CBF）自动调节功能。尽管AT1-AA通常在产后8年内一直保持升高状态，但其对产后CBF自动调节功能的影响尚不清楚。本研究调查了孕期AT1-AA升高是否会损害产后CBF自动调节功能，以及产后输注AT1-AA是否会加剧这种损害。从妊娠第14天开始，将AT1-AA注入12周龄的定时妊娠Sprague Dawley大鼠体内。在妊娠第18天测量子宫动脉阻力指数（UARI），作为与PE相关的内皮功能障碍的指标。让母鼠分娩。一组在产后9周接受第二次AT1-AA输注（50%围产期剂量，模拟产后PE女性中观察到的水平）。在产后第10周后，测量清醒大鼠的平均动脉压（MAP），并通过激光多普勒血流仪测量CBF自动调节功能。孕期的AT1-AA增加了UARI（P<0.05）。孕期的AT1-AA对产后MAP没有影响，但确实损害了产后CBF自动调节功能。产后输注AT1-AA显著升高了血压（P<0.01），但没有进一步损害CBF自动调节功能。本研究表明，孕期循环中的AT1-AA会导致产后很长一段时间内CBF自动调节功能受损，这表明AT1-AA升高会导致长期的脑血管后果。针对AT1-AA可能预防孕期和产后与PE相关的脑血管影响。
