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

Abstract

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.

The role of ACE2, angiotensin-(1–7) and Mas1 receptor axis in glucocorticoid-induced intrauterine growth restriction

“…This result is consistent with previous findings [27,34,35] indicating that the system tends to produce more Ang-(1-7) in late pregnancy possibly in an attempt to cause vasodilation and increase blood flow to the rapidly growing fetus late in gestation.…”

“…In early pregnancy, circulating levels of angiotensinogen, renin activity and Ang II are elevated [24,25]. Binding of Ang II to its receptor AT1 stimulates decidualization and rapid trophoblast proliferation in early pregnancy indicating a role of Ang II in implantation [26][27][28]. On the other hand, in mid to late pregnancy, an increase in urinary and plasma levels of Ang-(1-7) and ACE2 were found as well as an increase in local placental/ uterine production and activity of ACE2 suggesting a role for Ang-(1-7) in the enhancement of placental-fetal blood flow and rapid fetal growth in mid to late gestation [29][30][31][32][33].…”

Protective regulation of the ACE2/ACE gene expression by estrogen in human atrial tissue from elderly men

“…Accordingly, ACE2 mRNA and activity were increased in the kidney and uterus of pregnant animals. [38][39][40][41] In line with these results, Shenoy et al Our study indicates that E2 via down-regulation of ACE and simultaneous induction of ACE2 might modify the atrial responses to stress and could contribute to antiarrhythmic effects. The activated classical RAS and, in particular, increased AngII levels are key mediators of atrial tissue remodeling that might facilitate the development of atrial arrhythmia, like AF.…”

Regulation of renin-angiotensin system in gestational hypertension

“…In early pregnancy, Ang II promotes decidualization and rapid trophoblast proliferation mainly by binding to its receptor, AT1 [23]. In mid and late pregnancy, ACE, ACE2 and Ang (1-7) were elevated, which correlate with expanded maternal blood space and progressive fetal capillary development [10,24,25]. The dysregulation of RAS in placenta is associated with preeclampsia and other pathophysiological conditions during pregnancy.…”

“…Anton et al [9] reports in a clinical trial that AT1R mRNA and Ang II level was significantly higher in preeclampsia patients compared with normal pregnancies, despite a decrease in circulating Ang II. And Ang (1-7) concentrations decreased both in the uterus and placenta in the rat preeclampsia model [10]. Those suggest that it is necessary to conduct further investigation.…”