title: Hypervolemia of pregnancy is not maintained in mice chronically overexpressing angiotensinogen.
abstract: OBJECTIVE
  Women who develop pre-eclampsia show significantly less hypervolemia of pregnancy, compared with controls. We have shown that chronically elevated angiotensinogen expression increases a woman's risk of developing pre-eclampsia. Our objective was to determine whether increased angiotensinogen expression is sufficient to cause failed hypervolemia.
  
  
  METHODS
  To isolate the effects of elevated angiotensinogen expression, we studied transgenic mice with either 2 or 3 copies of the murine angiotensinogen gene. Plasma volume was measured by Evans blue dye dilution, and kidney sections were immunostained for angiotensinogen and renin.
  
  
  RESULTS
  Three-copy mice failed to maintain hypervolemia after midgestation (P < .01) and failed to up-regulate renin expression in the distal nephron, compared with 2-copy controls. Intrarenal angiotensinogen was up-regulated during pregnancy in both genotypes.
  
  
  CONCLUSIONS
  Chronically elevated angiotensinogen expression is sufficient to cause failed hypervolemia of pregnancy. Whether this observation is related to failed up-regulation of distal tubule renin expression requires further study.
authors.affiliation: Department of Human Genetics, University of Utah Health Sciences Center, Salt Lake City, UT, USA. morgante@ohsu.edu
authors.forename: Terry K
authors.initials: TK
authors.lastname: Morgan
authors.forename: Andreas
authors.initials: A
authors.lastname: Rohrwasser
authors.forename: Ling
authors.initials: L
authors.lastname: Zhao
authors.forename: Elaine
authors.initials: E
authors.lastname: Hillas
authors.forename: Tong
authors.initials: T
authors.lastname: Cheng
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Ward
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Lalouel
mesh_terms: D000808:Angiotensinogen / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001810:Blood Volume; D005260:Female; D018628:Gene Dosage; D005838:Genotype; D005865:Gestational Age; D007668:Kidney / Q000378:metabolism; D007685:Kidney Tubules, Collecting / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism / Q000502:physiology*; D012083:Renin / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000808:Angiotensinogen; D012083:Renin