The Uterine Placental Bed Renin-Angiotensin System in Normal and Preeclamptic Pregnancy

Abstract

Previously, we demonstrated activation of the renin-angiotensin system in the fetal placental chorionic villi, but it is unknown whether the immediately adjacent area of the maternal uterine placental bed is regulated similarly. This study measured angiotensin peptides, renin-angiotensin system component mRNAs, and receptor binding in the fundus from nonpregnant subjects (n = 19) and in the uterine placental bed from normal (n = 20) and preeclamptic (n = 14) subjects. In the uterine placental bed from normal pregnant women, angiotensin II peptide levels and angiotensinogen, angiotensin-converting enzyme, angiotensin receptor type 1 (AT(1)), AT(2), and Mas mRNA expression were lower as compared with the nonpregnant subjects. In preeclamptic uterine placental bed, angiotensin II peptide levels and renin and angiotensin-converting enzyme mRNA expression were significantly higher than normal pregnant subjects. The AT(2) receptor was the predominant receptor subtype in the nonpregnant fundus, whereas all angiotensin receptor binding was undetectable in normal and preeclamptic pregnant uterine placental bed compared with nonpregnant fundus. These findings suggest that the maternal uterine placental bed may play an endocrine role by producing angiotensin II, which acts in the adjacent placenta to vasoconstrict fetal chorionic villi vessels where we have shown previously that AT(1) receptors predominate. This would lead to decreased maternal-fetal oxygen exchange and fetal nutrition, a known characteristic of preeclampsia.

Alterations in the Renin-Angiotensin System in a Rat Model of Human Preeclampsia

“…The increased concentration of Ang II may act in the adjacent placenta within the fetal chorionic villi vessels [38]. This could contribute to the pathophysiology of preeclampsia by decreasing the maternal-fetal exchange of oxygen and nutrients [37,38]. In the present study, placental AT 1 receptor expression was found to be significantly higher in PDS and NPM rats compared to NP and PDSR (fig.…”

“…The villi are an indispensable component of the placenta that are responsible for maternal-fetal oxygen and nutrient transport. Anton et al [38] also demonstrated that the maternal uterine placental bed may play an endocrine role by producing Ang II. The increased concentration of Ang II may act in the adjacent placenta within the fetal chorionic villi vessels [38].…”

“…Anton et al [38] also demonstrated that the maternal uterine placental bed may play an endocrine role by producing Ang II. The increased concentration of Ang II may act in the adjacent placenta within the fetal chorionic villi vessels [38]. This could contribute to the pathophysiology of preeclampsia by decreasing the maternal-fetal exchange of oxygen and nutrients [37,38].…”

The effects of gestational age and maternal hypoxia on the placental renin angiotensin system in the mouse

“…The existence of components of the RAS within the placenta has been demonstrated previously in multiple animal species [19,21,34,35] but its temporal expression prolife has not been studied in the mouse which is frequently utilised to investigate the effects of maternal insults on fetal/placental development and long term disease. The current study shows for the first time, the placental mRNA levels of key components of the RAS in male and female fetuses across pregnancy.…”

“…Maternal perturbations such as hypoxia and dietary protein restriction have both been shown to alter placental renin levels [18,19], and placental insufficiency is associated with increased expression of many RAS genes [20]. Furthermore, an increase in the peptide levels of Angiotensin II and the mRNA levels of Ren and Ace in preeclamptic placentas suggests that the RAS may play a role in the pathophysiology of preeclampsia [21].…”