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Effects of Circulating and Local Uteroplacental Angiotensin II in Rat Pregnancy.

Hering, L; Herse, F; Geusens, N; Verlohren, S; Wenzel, K; Staff, AC; Brosnihan, KB; Huppertz, B; Luft, FC; Muller, DN; et al. Hering, L; Herse, F; Geusens, N; Verlohren, S; Wenzel, K; Staff, AC; Brosnihan, KB; Huppertz, B; Luft, FC; Muller, DN; Pijnenborg, R; Cartwright, JE; Dechend, R (2010) Effects of Circulating and Local Uteroplacental Angiotensin II in Rat Pregnancy. HYPERTENSION, 56 (2). 311 - 318 (8). ISSN 0194-911X https://doi.org/10.1161/HYPERTENSIONAHA.110.150961
SGUL Authors: Cartwright, Judith Eleanor

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Abstract

The renin-angiotensin (Ang) system is important during placental development. Dysregulation of the renin-Ang system is important in preeclampsia (PE). Female rats transgenic for the human angiotensinogen gene crossed with males transgenic for the human renin gene develop the PE syndrome, whereas those of the opposite cross do not. We used this model to study the role of Ang II in trophoblast invasion, which is shallow in human PE but deeper in this model. We investigated the following groups: PE rats, opposite-cross rats, Ang II–infused rats (1000 ng/kg per day), and control rats. Ang II infusion increased only circulating Ang II levels (267.82 pg/mL), opposite cross influenced only uteroplacental Ang II (13.52 fmol/mg of protein), and PE increased both circulating (251.09 pg/mL) and uteroplacental (19.24 fmol/mg of protein) Ang II. Blood pressure and albuminuria occurred in the models with high circulating Ang II but not in the other models. Trophoblast invasion increased in PE and opposite-cross rats but not in Ang II–infused rats. Correspondingly, uterine artery resistance index increased in Ang II–infused rats but decreased in PE rats. We then studied human trophoblasts and villous explants from first-trimester pregnancies with time-lapse microscopy. Local Ang II dose-dependently increased migration by 75%, invasion by 58%, and motility by 282%. The data suggest that local tissue Ang II stimulates trophoblast invasion in vivo in the rat and in vitro in human cells, a hitherto fore unrecognized function. Conceivably, upregulation of tissue Ang II in the maternal part of the placenta represents an important growth factor for trophoblast invasion and migration.

Item Type: Article
Additional Information: PubMed ID: 20530295
Keywords: Angiotensin II, Angiotensinogen, Animals, Animals, Genetically Modified, Brain, Cell Movement, Crosses, Genetic, Female, Fetal Growth Retardation, Humans, Liver, Male, Placenta, Pre-Eclampsia, Pregnancy, Pregnancy, Animal, Rats, Renin, Trophoblasts, Up-Regulation, Uterus, Science & Technology, Life Sciences & Biomedicine, Peripheral Vascular Disease, Cardiovascular System & Cardiology, preeclampsia, angiotensin II, transgenic rats, trophoblasts, decidua, placenta, vascular remodeling, ENDOVASCULAR TROPHOBLAST INVASION, AT1 RECEPTOR ACTIVATION, AGONISTIC AUTOANTIBODIES, MESOMETRIAL TRIANGLE, SPIRAL ARTERIES, PREECLAMPSIA, RENIN, MODEL, SYSTEM, HYPERTENSION, preeclampsia, angiotensin II, transgenic rats, trophoblasts, decidua, placenta, vascular remodeling
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Vascular (INCCVA)
Journal or Publication Title: HYPERTENSION
ISSN: 0194-911X
Related URLs:
Dates:
DateEvent
1 August 2010Published
Web of Science ID: WOS:000279880200024
URI: https://openaccess.sgul.ac.uk/id/eprint/100990
Publisher's version: https://doi.org/10.1161/HYPERTENSIONAHA.110.150961

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