The angiotensin II type i receptor contributes to impaired cerebral blood flow autoregulation caused by placental ischemia in pregnant rats

Junie P. Warrington, Fan Fan, Jeremy Duncan, Mark W. Cunningham, Babette B. Lamarca, Ralf Dechend, Gerd Wallukat, Richard J. Roman, Heather A. Drummond, Joey P. Granger, Michael J. Ryan

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Background: Placental ischemia and hypertension, characteristic features of preeclampsia, are associated with impaired cerebral blood flow (CBF) autoregulation and cerebral edema. However, the factors that contribute to these cerebral abnormalities are not clear. Several lines of evidence suggest that angiotensin II can impact cerebrovascular function; however, the role of the renin angiotensin system in cerebrovascular function during placental ischemia has not been examined. We tested whether the angiotensin type 1 (AT1) receptor contributes to impaired CBF autoregulation in pregnant rats with placental ischemia caused by surgically reducing uterine perfusion pressure. Methods: Placental ischemic or sham operated rats were treated with vehicle or losartan from gestational day (GD) 14 to 19 in the drinking water. On GD 19, we assessed CBF autoregulation in anesthetized rats using laser Doppler flowmetry. Results: Placental ischemic rats had impaired CBF autoregulation that was attenuated by treatment with losartan. In addition, we examined whether an agonistic autoantibody to the AT1 receptor (AT1-AA), reported to be present in preeclamptic women, contributes to impaired CBF autoregulation. Purified rat AT1-AA or vehicle was infused into pregnant rats from GD 12 to 19 via mini-osmotic pumps after which CBF autoregulation was assessed. AT1-AA infusion impaired CBF autoregulation but did not affect brain water content. Conclusions: These results suggest that the impaired CBF autoregulation associated with placental ischemia is due, at least in part, to activation of the AT1 receptor and that the RAS may interact with other placental factors to promote cerebrovascular changes common to preeclampsia.

Original languageEnglish (US)
Article number58
JournalBiology of Sex Differences
Issue number1
StatePublished - Dec 11 2019
Externally publishedYes


  • AT1-AA
  • Cerebral blood flow autoregulation
  • Losartan
  • Pregnancy

ASJC Scopus subject areas

  • Gender Studies
  • Endocrinology


Dive into the research topics of 'The angiotensin II type i receptor contributes to impaired cerebral blood flow autoregulation caused by placental ischemia in pregnant rats'. Together they form a unique fingerprint.

Cite this