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Cerebrovascular Function is Impaired in Offspring from a Pre‐Clinical Rat Model of Preeclampsia that Exhibits Sex‐Dependent Changes in Blood Pressure
Author(s) -
Cunningham Mark W,
Pabbidi Mallikarjuna R,
Williams Jan,
Duncan Jeremy W
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.05683
Subject(s) - blood pressure , offspring , medicine , preeclampsia , cerebral blood flow , cerebral autoregulation , cerebral perfusion pressure , autoregulation , phenylephrine , endocrinology , cardiology , pregnancy , anesthesia , biology , genetics
Background Adult offspring (AOS) born from hypertensive mothers have an increased risk of developing hypertension, stroke, and neurological complications later in life. Women with preeclampsia (PE) and the pre‐clinical RUPP (reduced uterine perfusion pressure) rat model of PE have an increase in blood pressure, impaired cerebral blood flow (CBF) autoregulation, and cerebrovascular dysfunction during pregnancy. Studies have shown that blood pressure is elevated early in male AOS and later in female AOS born from RUPP dams. However, no study has examined the cerebrovascular function in AOS from RUPP dams. Hypothesis We hypothesize that AOS from RUPP dams will exhibit impaired cerebral vascular myogenic responses and CBF autoregulation. Methods Male and female Sprague Dawley rats were born from normal pregnant (NP) and RUPP dams. After 3 weeks of weening, OS rats were separated by sex and groups determined by their mother. OS rats were aged to 17 weeks and mean arterial pressure (MAP) and body weight (BW) was recorded. At 22–23 weeks of age, myogenic responses were determined by changes in vascular diameter of the middle cerebral artery in response to increases in intraluminal pressure. At 29–30 weeks, CBF autoregulation was measured by laser doppler flowmetry through a 4 mm x 4 mm cranial window under anesthesia. MAP was elevated step‐wise from 100–190 mmHg by infusion of phenylephrine to determine changes in CBF. Results At 17 weeks, BW was smaller in male AOS born from RUPP vs NP (381±10 vs 414±3g, p<0.05). No change was observed in female AOS BWs. MAP was elevated in male AOS RUPP vs NP (143±2 vs 133±3 mmHg, p<0.05) at 17 weeks, with no change in female AOS. At 22–23 weeks, the myogenic response was impaired and tone was increased in male AOS RUPP vs NP (p<0.05). At 29–30 weeks, CBF autoregulation was impaired in male OS RUPP vs NP rats at 120 mmHg (129±12% vs 103±4), at 140 mmHg (149±21 vs 107±12%), and at 160 mmHg (172±31 vs 108±15%) respectively. Interestingly, CBF autoregulation was also impaired in female AOS RUPP vs NP rats at 140 mmHg (130±14 vs 110±18%) and 160 mmHg (175±2 vs 99±8%, p<0.05) in the absence of hypertension. Conclusion A decrease in BW, increase in blood pressure, and impairments of CBF autoregulation was observed in male RUPP AOS. In contrast, female RUPP AOS exhibited no changes in body weight or blood pressure, but showed a marked impairment in CBF autoregulation, suggesting that elevated MAP is not a prerequisite or required for impaired CBF autoregulation in females. Future studies are warranted to examine the mechanisms underlying CBF autoregulation impairment and their associated sex differences in AOS born from hypertensive pregnancies associated with placental ischemia. Support or Funding Information Supported: AHA18CDA34110264