TY - JOUR
T1 - The angiotensin II type i receptor contributes to impaired cerebral blood flow autoregulation caused by placental ischemia in pregnant rats
AU - Warrington, Junie P.
AU - Fan, Fan
AU - Duncan, Jeremy
AU - Cunningham, Mark W.
AU - Lamarca, Babette B.
AU - Dechend, Ralf
AU - Wallukat, Gerd
AU - Roman, Richard J.
AU - Drummond, Heather A.
AU - Granger, Joey P.
AU - Ryan, Michael J.
N1 - Funding Information:
This study was supported by the NIH/NHLBI (HL136684, HL129192, P01HL051971, T32HL105324), NIH/NIGMS (P20GM104357, U54GM115428), and the American Heart Association (13POST16240000). The content is solely the responsibility of the author and does not necessarily represent the official views of the National Institutes of Health or American Heart Association.
Publisher Copyright:
© 2019 The Author(s).
PY - 2019/12/11
Y1 - 2019/12/11
N2 - 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.
AB - 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.
KW - AT1-AA
KW - Cerebral blood flow autoregulation
KW - Losartan
KW - Pregnancy
UR - http://www.scopus.com/inward/record.url?scp=85076378221&partnerID=8YFLogxK
U2 - 10.1186/s13293-019-0275-1
DO - 10.1186/s13293-019-0275-1
M3 - Article
C2 - 31829239
AN - SCOPUS:85076378221
SN - 2042-6410
VL - 10
JO - Biology of Sex Differences
JF - Biology of Sex Differences
IS - 1
M1 - 58
ER -