Increased Angiotensin II in the Mesometrial Triangle of a Transgenic Rat Model of Preeclampsia

Abstract

The pregnant female human angiotensinogen ( h AGN) transgenic rat mated with the male h renin ( h REN) transgenic rat is a model of preeclampsia with increased blood pressure, proteinuria, and placenta alterations of edema and necrosis. The reverse mating of female h REN×male h AGN does not show preeclamptic features. Because the placenta is well-recognized to be a key contributor to the preeclamptic syndrome, our hypothesis is that local angiotensin peptide concentrations found in the placenta and its associated mesometrial triangle of the preeclamptic transgenic rat differ from the reverse mating. We characterized the angiotensin peptide content and the mRNA expression of h REN and h AGN of the mesometrial triangle and the placenta. Three groups of pregnant rats from the matings (Sprague-Dawley×Sprague-Dawley, reverse mating, and female h AGN×male h REN) were studied on day 21 of gestation. In the h AGN× h REN transgenic rat, angiotensin II is significantly increased in the placenta and mesometrial triangle vs Sprague-Dawley (24.2±3.9 vs 8.6±1.5 pg/mg protein; 27.8±5.5 vs 5.6±1.3 pg/mg protein; P <0.05), whereas in the reverse mating angiotensin II is increased in the placenta (19.1±1.7 vs 5.6±1.3 pg/mg protein; P <0.05) but unchanged in the mesometrial triangle (4.2±0.2 vs 8.6±1.5 pg/mg protein). The marked contrast in the expression of angiotensin II in the mesometrial triangle of the preeclamptic model vs the reverse mating suggests that local angiotensin II generated from the maternal parts of the uteroplacental unit may play a critical role in preeclampsia.