Renin-angiotensin system in normal pregnancy and in preeclampsia: A comprehensive review

•The Renin Angiotensin System plays an important role for the evolution of pregnancy under physiological conditions.•Pregnant women develop resistance to the vasopressor effects of Angiotensin II.•The levels of renin, Angiotensin II and aldosterone are abnormally decreased in preeclampsia when compared to normal pregnancies.•The expression and activity of angiotensin type 1 receptors are excessively increased in preeclampsia.•Angiotensin-(1–7) was reduced in the uterus and placenta of rats with preeclampsia compared to normal pregnant ones. The activation of the Renin Angiotensin System (RAS) is required during pregnancy and it seems that RAS dysfunction has some important effects on pathological pregnancy conditions, including preeclampsia (PE). The objective of this review is to summarize and to discuss the role of the RAS in normal pregnancy and in PE. We found evidence that the RAS is important for the evolution of pregnancy under physiological conditions and plays an important role in the pathogenesis of PE. In normal gestation, almost all circulating components of RAS are increased and there is a general state of non-reactivity to the vasoconstrictor actions of Angiotensin (Ang) II. In PE, changes in the circulating levels of RAS components occur, especially with an intense decrease in the levels of Ang I, Ang II and Ang-(1–7). Our findings endorse the idea that PE is a disease whose cornerstone relies on altered placental physiology. There are high tissue levels of Ang II type 1 receptor (AT1R) in the musculature of the blood vessels and in the placenta, generating a state of increased sensitivity to the vasoconstrictor action of Ang II. AT1R autoantibodies (AT1R-AA) might be one of the key points for the vicious cycle of PE, as these molecules are synthesized in situations of hypoxia and enhance placental vasoconstriction, causing even more hypoxia. Further studies are needed to investigate the role of circulating RAS, uteroplacental RAS and local RAS molecules from other tissues related to the pathogenesis of PE.