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1 Hypertension and Vascular Research Center, Wake Forest Univeristy School of Medicine, Winton-Salem, North Carolina, United States
2 Department of Nephrology, Catholic University of Medicine Faculty of Medicine, Santiago, Chile
3 Department of Obstetrics and Gynecology, Wake Forest Univeristy School of Medicine, United States
* To whom correspondence should be addressed. E-mail: bbrosnih{at}wfubmc.edu.
The present study was designed to determine angiotensin peptide content [Ang I, Ang II Ang-(1-7)], ACE2 mRNA and the immunocytochemical distribution of Ang-(1-7) and ACE2 in the utero-embryonic 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 was 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, amniotic and yolk sac epithelium. Uterine Ang II concentration at early pregnancy was significantly decreased by 21-55% in the implantation and inter-implantation sites as compared to virgin rats, whereas Ang-(1-7) levels were maintained at pre-pregnancy 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 as compared to virgin rats, yet within the implantation site it was down-regulated. 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.
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