Hypervolemia of pregnancy is not maintained in mice chronically overexpressing angiotensinogen.
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.
Morgan
Terry K
TK
Department of Human Genetics, University of Utah Health Sciences Center, Salt Lake City, UT, USA. morgante@ohsu.edu
Rohrwasser
Andreas
A
Zhao
Ling
L
Hillas
Elaine
E
Cheng
Tong
T
Ward
Kenneth J
KJ
Lalouel
Jean-Marc
JM
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
D000808:Angiotensinogen; D012083:Renin