Abstract P101: AT1-AA Induced Hypertension During Pregnancy Decreases Maternal Cerebral Blood Flow Autoregulation Postpartum

Abstract

Preeclampsia (PE), new-onset hypertension during pregnancy, is the leading cause of morbidity and mortality for the mother and is associated with multi-organ dysfunction including the brain. 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); therefore, we believe it to play a role in PE pathophysiology and the increased incidents of cardiovascular disorders PP. Although 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, we don’t know the effects of AT1-AA on MAP and CBF hemodynamics in the PP period. 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 on gestational day (GD) 14 via a mini-osmotic pump. Dams were allowed to deliver; 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 PP week 12, MAP was 118±3 mmHg in NP (n=4), 119±2 mmHg in AT1-AA (n=5), and 126±5 in AT1-AA + AT1-AA (1:80) PP (P<0.05, n=5). CBF increased by 43±8% (P<0.05, n=2) in rats with AT1-AA during pregnancy and by 37±9% (P<0.05, n=4) in rats with AT1-AA during pregnancy and (1:80) PP in response to increased MAP from 100 to 140 mmHg, versus only 6±2% (n=3) in normal pregnant controls. In conclusion, AT1-AA during pregnancy causes sustained changes in CBF hemodynamics PP. Sustained maternal AT1-AA PP also causes increased blood pressures long-term in association with impaired CBF. These data indicate that perinatal and PP AT1-AA cause long-term cardiovascular and cerebrovascular consequences for PE women.