PMID- 31266978 OWN - NLM STAT- MEDLINE DCOM- 20201022 LR - 20211204 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 9 IP - 1 DP - 2019 Jul 2 TI - Characterisation of the Selective Reduced Uteroplacental Perfusion (sRUPP) Model of Preeclampsia. PG - 9565 LID - 10.1038/s41598-019-45959-6 [doi] LID - 9565 AB - Preeclampsia is a complication of pregnancy characterised by gestational hypertension, proteinuria and/or end organ disease. The reduced uteroplacental perfusion (RUPP) model, via partial occlusion of the lower abdominal aorta, mimics insufficient placental perfusion as a primary causal characteristic of preeclampsia. However, a major limitation of the RUPP model is that perfusion is reduced to the entire hindquarters of the rat resulting in hindlimb ischemia. We hypothesised that clipping the uterine and ovarian arteries in the selective (s)RUPP model would provoke signs of preeclampsia while avoiding systemic ischemia. Sham, RUPP or sRUPP procedures were performed in pregnant Sprague Dawley rats on gestational day (GD)14. On GD21 uterine blood flow was significantly reduced in both the RUPP and sRUPP models while aortic flow was reduced only in RUPP. Both models resulted in increased MAP, increased vascular oxidative stress (superoxide generation), increased pro-inflammatory (RANTES) and reduced pro-angiogenic (endoglin) mediators. Vascular compliance and constriction were unaltered in either RUPP or sRUPP groups. In summary, refinements to the RUPP model simultaneously maintain the characteristic phenotype of preeclampsia and avoid peripheral ischemia; providing a useful tool which may be used to increase our knowledge and bring us closer to a solution for women affected by preeclampsia. FAU - Morton, J S AU - Morton JS AD - Faculty of Medicine and Dentistry, Dept. of Ob/Gyn, University of Alberta, Edmonton, AB, T6G 2S2, Canada. AD - Women and Children's Health Research Institute, Edmonton, AB, T6G 2R3, Canada. FAU - Levasseur, J AU - Levasseur J AD - Faculty of Medicine and Dentistry, Dept. of Pediatrics, University of Alberta, Edmonton, AB, T6G 2S2, Canada. FAU - Ganguly, E AU - Ganguly E AD - Faculty of Medicine and Dentistry, Dept. of Ob/Gyn, University of Alberta, Edmonton, AB, T6G 2S2, Canada. AD - Faculty of Medicine and Dentistry, Dept. of Physiology, University of Alberta, Edmonton, AB, T6G 2H7, Canada. AD - Women and Children's Health Research Institute, Edmonton, AB, T6G 2R3, Canada. FAU - Quon, A AU - Quon A AUID- ORCID: 0000-0003-2334-4618 AD - Faculty of Medicine and Dentistry, Dept. of Ob/Gyn, University of Alberta, Edmonton, AB, T6G 2S2, Canada. AD - Women and Children's Health Research Institute, Edmonton, AB, T6G 2R3, Canada. FAU - Kirschenman, R AU - Kirschenman R AD - Faculty of Medicine and Dentistry, Dept. of Ob/Gyn, University of Alberta, Edmonton, AB, T6G 2S2, Canada. AD - Women and Children's Health Research Institute, Edmonton, AB, T6G 2R3, Canada. FAU - Dyck, J R B AU - Dyck JRB AD - Faculty of Medicine and Dentistry, Dept. of Pediatrics, University of Alberta, Edmonton, AB, T6G 2S2, Canada. FAU - Fraser, G M AU - Fraser GM AD - Division of Biomedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, A1B 3V6, Canada. FAU - Davidge, S T AU - Davidge ST AD - Faculty of Medicine and Dentistry, Dept. of Ob/Gyn, University of Alberta, Edmonton, AB, T6G 2S2, Canada. sandra.davidge@ualberta.ca. AD - Faculty of Medicine and Dentistry, Dept. of Physiology, University of Alberta, Edmonton, AB, T6G 2H7, Canada. sandra.davidge@ualberta.ca. AD - Women and Children's Health Research Institute, Edmonton, AB, T6G 2R3, Canada. sandra.davidge@ualberta.ca. LA - eng GR - MOP132320/CIHR/Canada GR - FS154313/CIHR/Canada GR - MOP133675/CIHR/Canada PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190702 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Biomarkers) RN - 0 (Cytokines) RN - 0 (Inflammation Mediators) SB - IM MH - Animals MH - Biomarkers MH - Blood Pressure MH - Cytokines/blood/metabolism MH - *Disease Susceptibility MH - Female MH - Inflammation Mediators MH - *Models, Biological MH - Oxidative Stress MH - Placenta/*blood supply/*metabolism MH - Pre-Eclampsia/diagnosis/*etiology/*metabolism/physiopathology MH - Pregnancy MH - Pregnancy Outcome MH - Proteinuria MH - Rats MH - Regional Blood Flow MH - Translational Research, Biomedical MH - Uterus/*blood supply/*metabolism PMC - PMC6606748 COIS- The authors declare no competing interests. EDAT- 2019/07/04 06:00 MHDA- 2020/10/23 06:00 PMCR- 2019/07/02 CRDT- 2019/07/04 06:00 PHST- 2019/02/12 00:00 [received] PHST- 2019/06/20 00:00 [accepted] PHST- 2019/07/04 06:00 [entrez] PHST- 2019/07/04 06:00 [pubmed] PHST- 2020/10/23 06:00 [medline] PHST- 2019/07/02 00:00 [pmc-release] AID - 10.1038/s41598-019-45959-6 [pii] AID - 45959 [pii] AID - 10.1038/s41598-019-45959-6 [doi] PST - epublish SO - Sci Rep. 2019 Jul 2;9(1):9565. doi: 10.1038/s41598-019-45959-6.