AT1-AA Exposure During Pregnancy Impairs Maternal Cerebral Blood Flow Autoregulation Postpartum
Authors: Campbell Nathan , Strong Luke , Fang Xing , Border Jane , Herrock Owen , Turner Ty , Deer Evangeline , Amaral Lorena , Roman Richard , LaMarca Babbette 
Published: May 2023

Preeclampsia (PE), new-onset hypertension during pregnancy, is the leading cause of morbidity and mortality for the mother and the fetus. A leading cause of mortality during PE is cerebrovascular disease. Women with PE have activated B cells producing agonistic autoantibodies to the angiotensin II type 1 receptor (AT1-AA) which remain elevated in maternal circulation up to 8 years postpartum (PP). AT1-AA contributes to endothelial dysfunction in the kidney, placenta, and brain during pregnancy. We believe it plays a role in the increased incidents of cardiovascular and cerebrovascular disorders in PP PE women. We have shown at AT1-AA infusion into pregnant rats results in elevated mean arterial pressure (MAP), impaired cerebral blood flow (CBF) autoregulation, and reduced pup weight. However, the effects of perinatal AT1-AA and sustained AT1-AA PP on MAP and CBF hemodynamics in the PP period is unknown. We hypothesize that AT1-AA induced hypertension during pregnancy will cause maternal hypertension and impaired maternal CBF PP.To test this hypothesis, AT1-AA (1:40) was infused into pregnant Sprague Dawley rats on gestational day (GD) 14 via a mini-osmotic pump. On GD18, uterine artery resistance index (UARI) was measured by Doppler ultrasound. Dams were allowed to deliver and pup weights were recorded within 12 hours. PP dams were aged to 9 weeks after birth and one group of AT1-AA PP dams received a second infusion of AT1-AA (1:80), to mimic the levels of AT1-AA seen in PP PE women. At 10 weeks PP, maternal MAP was measured and at 12 weeks PP, CBF autoregulation was measured by laser Doppler flowmeter.At GD 18, UARI was elevated in AT1-AA infused rats (0.610±0.080, n=7, P<0.05) compared to NP rats (0.475±0.070, n=5). At PP week 10, MAP was elevated in AT1-AA + AT1-AA (1:80) PP (129±1 mmHg, n=5, P<0.01) compared to NP (120±2 mmHg, n=5) and AT1-AA (120±1 mmHg, n=6). CBF increased by 34±4% (P<0.05, n=8) in rats with AT1-AA during pregnancy and by 39±4% (P<0.05, n=8) in rats with AT1-AA during pregnancy and (1:80) PP in response to increased MAP from 100 to 140 mmHg, versus only 4±3% (n=8) in normal pregnant controls.In conclusion, AT1-AA during pregnancy causes sustained changes in CBF hemodynamics PP. Increased AT1-AA PP also causes elevated blood pressures in association with impaired CBF. These data indicate that perinatal and PP AT1-AA cause long-term cardiovascular and cerebrovascular consequences for PE women. Targeting AT1-AA may prevent cerebral vascular and neurological defects in PE, and alleviate some of the long-term impact postpartum.

This study was supported in part by NIH grants HD067541 (BL), H13865 (RJR).and P20GM121334 (BL, LA)

This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.