Lower Middle Cerebral Artery Resistance In A Transgenic Rat Model Of Preeclampsia: A Platform For Studying Long-term Preeclampsia Induced Cerebrovascular Disease

Preeclampsia (PE) is a pregnancy disorder characterized by new onset hypertension and end-organ dysfunction. PE patients have increased risk of cerebrovascular disease (CVD) later in life; however, the mechanisms are unclear. We determined whether exposure to a PE-like syndrome in transgenic rat (TGA-PE: female TG for angiotensinogen mated to male TG for renin) alters left middle cerebral artery (LMCA) or left internal carotid (LICA) artery hemodynamics at 2 or 5 months post-pregnancy. The analyses of systolic (SBP) and diastolic (DBP) blood pressures and heart rate (HR) (by tail cuff; NIBP-8 Columbus Instruments), and LMCA and LICA pulsatility index (PI) (by transcranial Doppler (TCD); Vevo 2100), were performed at late gestation, and at 2 and 5 months post-pregnancy. SBP and DBP were elevated in TGA-PE vs. Sprague-Dawley (SD) in late pregnancy (n=5-6), and at 2 (n=4-6), and 5 months (n=2-3) post-pregnancy (p<0.05). HR was elevated in TGA-PE vs. SD in late pregnancy (493.5±10.6 vs. 392.5±14.2, p<0.05, n=5-6), but not at 2 or 5 months post-pregnancy. However, LMCA PI was lower in TGA-PE vs. SD at 2 months post-pregnancy (p<0.05), and tended to decrease in late gestation and at 5 months post-pregnancy. LICA PI was lower in TGA-PE vs. SD during pregnancy (0.729 ± 0.086 vs 1.34 ± 0.095, p<0.05, n=4-5). In summary, PE-like syndrome in TGA-PE resulted in higher SBP and lower LMCA resistance versus SD at 2 months post-pregnancy, suggesting a dysfunctional autoregulation of cerebral blood flow. Since women with history of PE have lower MCA resistance, we conclude that TGA-PE model may provide a suitable platform to investigate the mechanistic link between PE and future development of CVD.