Cerebral Blood Flow Autoregulation in Offspring From Experimentally Preeclamptic Rats and the Effect of Age

Abstract

Preeclampsia is a hypertensive disorder of pregnancy that causes significant, long term cardiovascular effects for both the mother and offspring. A previous study demonstrated that middle cerebral arteries in offspring from an experimental rat model of preeclampsia were smaller, stiffer, and did not enlarge over the course of maturation, suggesting potential hemodynamic alterations in these offspring. Here we investigated the effect of experimental preeclampsia on cerebral blood flow autoregulation in juvenile and adult offspring that were born from normal pregnant or experimentally preeclamptic rats. Relative cerebral blood flow was measured using laser Doppler flowmetry, and cerebral blood flow autoregulation curves were constructed by raising blood pressure and controlled hemorrhage to lower blood pressure. Immunohistochemistry was used to assess middle cerebral artery size. Heart rate and blood pressure were measured in awake adult offspring using implanted radiotelemetry. Serum epinephrine was measured using enzyme-linked immunosorbent assay. Offspring from both groups showed maturation of cerebral blood flow autoregulation as offspring aged from juvenile to adulthood as demonstrated by the wider autoregulatory plateau. Experimental preeclampsia did not affect cerebral blood flow autoregulation in juvenile offspring, and it had no effect on cerebral blood flow autoregulation in adult offspring over the lower range of blood pressures. However, experimental preeclampsia caused a right shift in the upper range of blood pressures in adult offspring (compared to normal pregnant). Structurally, middle cerebral arteries from normal pregnant offspring demonstrated growth with aging, while middle cerebral arteries from experimentally preeclamptic offspring did not, and by adulthood normal pregnant offspring had significantly larger middle cerebral arteries. Middle cerebral artery lumen diameters did not significantly change as offspring aged. Serum epinephrine was elevated in juvenile experimentally preeclamptic offspring, and a greater degree of hemorrhage was required to induce hypotension, suggesting increased sympathetic activity. Finally, despite no evidence of increased sympathetic activity, adult experimentally preeclamptic offspring were found to have persistently higher heart rate. These results demonstrate a significant effect of experimental preeclampsia on the upper range of autoregulation and cerebrovascular structure in juvenile and adult offspring that could have an important influence on brain perfusion under conditions of hypo and/or hypertension.

Reduced Brain Cortex Angiogenesis in the Offspring of the Preeclampsia-Like Syndrome

“…This may explain our previous findings of reduced cerebral blood flow observed in the motor and somatosensory cortex of P5-PELS. 10 Furthermore, these findings agree with previous reports 12,13 showing impaired brain vascular function in both the middle cerebral artery and vein of Galen after birth (postnatal days 16–30) in offspring from PELS. Nevertheless, our results contrast with another study in adult offspring (12 months of age) of PELS generated in transgenic female mice overexpressing human angiotensinogen and renin, which showed increased cerebral blood flow in response to whisker stimulation.…”

“…11 Animal studies have also shown defects in the structure and function of the middle cerebral artery in offspring from rat preeclampsia-like syndrome (PELS) model. 12,13 More recently, we found that mice (postnatal day 5 [P5]) of PELS (characterized by a reduction in placental perfusion) showed a significant decrease in brain perfusion, which may involve structural alterations in the brain microcirculation. 10 Vascular endothelial growth factor (VEGF), placental growth factor (PlGF), and VEGF receptors (VEGFRs) are critical regulators of angiogenesis.…”

Uterine Blood Flow Dynamic Changes in Sprague-Dawley Rats During Pregnancy Using Noninvasive Color Doppler Sonography

“…In rats most of literatures investigated the changes in the uterine blood flow during different models either for diabetes [27,28], preeclampsia [29,30] or the intrauterine fetal growth retardations [30][31][32][33]. Accordingly, the results of the present study regarding the investigation of uterine blood flow changes during normal pregnancy in rats would be considered as a references values for the uterine arteries Doppler indexes variation.…”