RGD Reference Report - Effects of circulating and local uteroplacental angiotensin II in rat pregnancy. - Rat Genome Database

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Effects of circulating and local uteroplacental angiotensin II in rat pregnancy.

Authors: Hering, Lydia  Herse, Florian  Geusens, Nele  Verlohren, Stefan  Wenzel, Katrin  Staff, Anne C  Brosnihan, K Bridget  Huppertz, Berthold  Luft, Friedrich C  Muller, Dominik N  Pijnenborg, Robert  Cartwright, Judith E  Dechend, Ralf 
Citation: Hering L, etal., Hypertension. 2010 Aug;56(2):311-8. doi: 10.1161/HYPERTENSIONAHA.110.150961. Epub 2010 Jun 7.
RGD ID: 13432363
Pubmed: PMID:20530295   (View Abstract at PubMed)
DOI: DOI:10.1161/HYPERTENSIONAHA.110.150961   (Journal Full-text)

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.




  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
AGTHumanFetal Growth Retardation  IMP  RGD 
AgtRatFetal Growth Retardation  ISOAGT (Homo sapiens) RGD 
AgtMouseFetal Growth Retardation  ISOAGT (Homo sapiens) RGD 
AGTHumanpre-eclampsia  IMP  RGD 
AgtRatpre-eclampsia  ISOAGT (Homo sapiens) RGD 
AgtMousepre-eclampsia  ISOAGT (Homo sapiens) RGD 


Genes (Rattus norvegicus)
Agt  (angiotensinogen)

Genes (Mus musculus)
Agt  (angiotensinogen)

Genes (Homo sapiens)
AGT  (angiotensinogen)