期刊
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
卷 195, 期 6, 页码 1700-1706出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.ajog.2006.04.005
关键词
kidney; intrarenal renin-angiotensin system; pregnancy; plasma volume; mouse
资金
- NCRR NIH HHS [M01-RR00064] Funding Source: Medline
- NHLBI NIH HHS [1R01-HL 45325] Funding Source: Medline
- NICHD NIH HHS [1R01-HD 32170-01] Funding Source: Medline
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. Study design: To isolate the effects of elevated angiotensinogen expression, we studied transgenic mice with either 2 or 3 copies of the in urine 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. Conclusion: 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. (c) 2006 Mosby, Inc. All rights reserved.
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