Placental Ischemia Impairs Middle Cerebral Artery Myogenic Responses in the Pregnant Rat

Abstract

One potential mechanism contributing to the increased risk for encephalopathies in women with preeclampsia is altered cerebral vascular autoregulation resulting from impaired myogenic tone. Whether placental ischemia, a commonly proposed initiator of preeclampsia, alters cerebral vascular function is unknown. This study tested the hypothesis that placental ischemia in pregnant rats (caused by reduced uterine perfusion pressure [RUPP]) leads to impaired myogenic responses in middle cerebral arteries. Mean arterial pressure was increased by RUPP (135±3 mm Hg) compared with normal pregnant rats (103±2 mm Hg) and nonpregnant controls (116±1 mm Hg). Middle cerebral arteries from rats euthanized on gestation day 19 were assessed in a pressure arteriograph under active (+Ca 2+ ) and passive (0 Ca 2+ ) conditions, whereas luminal pressure was varied between 25 and 150 mm Hg. The slope of the relationship between tone and pressure in the middle cerebral artery was 0.08±0.01 in control rats and was similar in normal pregnant rats (0.05±0.01). In the RUPP model of placental ischemia, this relationship was markedly reduced (slope=0.01±0.00; P <0.05). Endothelial dependent and independent dilation was not different between groups, nor was there evidence of vascular remodeling assessed by the wall:lumen ratio and calculated wall stress. The impaired myogenic response was associated with brain edema measured by percentage of water content (RUPP P <0.05 versus control and normal pregnant rats). This study demonstrates that placental ischemia in pregnant rats leads to impaired myogenic tone in the middle cerebral arteries and that the RUPP model is a potentially important tool to examine mechanisms leading to encephalopathy during preeclamptic pregnancies.