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This Article Full Text Full Text (PDF) All Versions of this Article: 294/1/R151    most recent 00514.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Neves, L. A. A. Articles by Brosnihan, K. B. Search for Related Content PubMed PubMed Citation Articles by Neves, L. A. A. Articles by Brosnihan, K. B.

DEVELOPMENTAL PHYSIOLOGY AND PREGNANCY

ACE2 and ANG-(1-7) in the rat uterus during early and late gestation

¹Hypertension and Vascular Research Center and ³Department of Obstetrics and Gynecology, Wake Forest University School of Medicine, Winston-Salem, North Carolina; and ²Department of Nephrology, Pontificia Universidad Catolica de Chile, Santiago, Chile

Submitted 15 July 2007 ; accepted in final form 29 October 2007

The present study was designed to determine ANG peptide content [ANG I, ANG II, ANG-(1-7)], ACE2 mRNA, and the immunocytochemical distribution of ANG-(1-7) and ACE2 in the uteroembryonic unit during early and late gestation in Sprague-Dawley rats and in a rat model of pregnancy-induced hypertension, the reduced uterine perfusion pressure (RUPP) model. At early pregnancy ANG-(1-7) and ACE2 staining were localized in the primary and secondary decidual zone and luminal and glandular epithelial cells. During late gestation, ANG-(1-7) and ACE2 staining was visualized in the labyrinth placenta and amniotic and yolk sac epithelium. Uterine ANG II concentration at early pregnancy was significantly decreased by 21–55% in the implantation and interimplantation sites compared with virgin rats, whereas ANG-(1-7) levels were maintained at prepregnancy levels. At late gestation, uterine concentrations of ANG I and ANG II were significantly increased (30% and 25%, respectively). In RUPP animals, ANG-(1-7) concentration is significantly reduced in the uterus (181 ± 16 vs. 372 ± 74 fmol/g of tissue) and placenta (143 ± 26 vs. 197 ± 20 fmol/g of tissue). ACE2 mRNA increased in the uterus of early pregnant compared with virgin rats, yet within the implantation site it was downregulated. At late pregnancy, ACE2 mRNA is elevated by 58% in the uterus and decreased by 59% in RUPP animals. The regulation of ANG-(1-7) and ACE2 in early and late pregnancy supports the hypothesis that ANG-(1-7) and ACE2 may act as a local autocrine/paracrine regulator throughout pregnancy, participating in the early (angiogenesis, apoptosis, and growth) and late (uteroplacental blood flow) events of pregnancy.

renin-angiotensin system; implantation

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