PMID- 31829239 OWN - NLM STAT- MEDLINE DCOM- 20200428 LR - 20240422 IS - 2042-6410 (Electronic) IS - 2042-6410 (Linking) VI - 10 IP - 1 DP - 2019 Dec 11 TI - The angiotensin II type I receptor contributes to impaired cerebral blood flow autoregulation caused by placental ischemia in pregnant rats. PG - 58 LID - 10.1186/s13293-019-0275-1 [doi] LID - 58 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. FAU - Warrington, Junie P AU - Warrington JP AD - Department of Physiology & Biophysics, University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS, 39216, USA. FAU - Fan, Fan AU - Fan F AD - Department of Physiology & Biophysics, University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS, 39216, USA. FAU - Duncan, Jeremy AU - Duncan J AD - Department of Physiology & Biophysics, University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS, 39216, USA. FAU - Cunningham, Mark W AU - Cunningham MW AD - Department of Physiology & Biophysics, University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS, 39216, USA. FAU - LaMarca, Babette B AU - LaMarca BB AD - Department of Physiology & Biophysics, University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS, 39216, USA. FAU - Dechend, Ralf AU - Dechend R AD - Experimental and Clinical Research Center and Max-Delbruck Center for Molecular Medicine, and HELIOS Clinic Berlin, Berlin, Germany. FAU - Wallukat, Gerd AU - Wallukat G AD - Experimental and Clinical Research Center and Max-Delbruck Center for Molecular Medicine, and HELIOS Clinic Berlin, Berlin, Germany. FAU - Roman, Richard J AU - Roman RJ AD - Department of Physiology & Biophysics, University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS, 39216, USA. FAU - Drummond, Heather A AU - Drummond HA AD - Department of Physiology & Biophysics, University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS, 39216, USA. FAU - Granger, Joey P AU - Granger JP AD - Department of Physiology & Biophysics, University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS, 39216, USA. FAU - Ryan, Michael J AU - Ryan MJ AUID- ORCID: 0000-0002-5679-6031 AD - Department of Physiology & Biophysics, University of Mississippi Medical Center, 2500 N. State Street, Jackson, MS, 39216, USA. mjryan@umc.edu. LA - eng GR - R01 HL136684/HL/NHLBI NIH HHS/United States GR - R01 AG057842/AG/NIA NIH HHS/United States GR - P20 GM104357/GM/NIGMS NIH HHS/United States GR - R00 HL129192/HL/NHLBI NIH HHS/United States GR - R01 HL138685/HL/NHLBI NIH HHS/United States GR - P20 GM121334/GM/NIGMS NIH HHS/United States GR - U54 GM115428/GM/NIGMS NIH HHS/United States GR - P01 HL051971/HL/NHLBI NIH HHS/United States GR - T32 HL105324/HL/NHLBI NIH HHS/United States GR - R21 AG050049/AG/NIA NIH HHS/United States GR - K99 HL129192/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20191211 PL - England TA - Biol Sex Differ JT - Biology of sex differences JID - 101548963 RN - 0 (Angiotensin II Type 1 Receptor Blockers) RN - 0 (Receptor, Angiotensin, Type 1) RN - JMS50MPO89 (Losartan) SB - IM MH - Angiotensin II Type 1 Receptor Blockers/pharmacology MH - Animals MH - *Cerebrovascular Circulation MH - Female MH - *Homeostasis MH - Ischemia/*physiopathology MH - Losartan/pharmacology MH - Placenta/*blood supply MH - Pre-Eclampsia/physiopathology MH - Pregnancy MH - Rats, Sprague-Dawley MH - Receptor, Angiotensin, Type 1/*physiology PMC - PMC6907203 OTO - NOTNLM OT - AT1-AA OT - Cerebral blood flow autoregulation OT - Losartan OT - Pregnancy COIS- The authors declare that they have no competing interests. EDAT- 2019/12/13 06:00 MHDA- 2020/04/29 06:00 PMCR- 2019/12/11 CRDT- 2019/12/13 06:00 PHST- 2019/08/20 00:00 [received] PHST- 2019/11/29 00:00 [accepted] PHST- 2019/12/13 06:00 [entrez] PHST- 2019/12/13 06:00 [pubmed] PHST- 2020/04/29 06:00 [medline] PHST- 2019/12/11 00:00 [pmc-release] AID - 10.1186/s13293-019-0275-1 [pii] AID - 275 [pii] AID - 10.1186/s13293-019-0275-1 [doi] PST - epublish SO - Biol Sex Differ. 2019 Dec 11;10(1):58. doi: 10.1186/s13293-019-0275-1.