The uteroplacental renin-angiotensin system: a review

Abstract

Evidence has accumulated for the existence of local tissue renin-angiotensin systems in the reproductive tissues. In the ovary the local renin-angiotensin system (RAS) has been shown to influence ovulation and steroidogenesis. In this review we focus on aspects of a local RAS in the uteroplacental unit. High renin concentrations have been found in all tissues of the uteroplacental unit. The presence of renin mRNA in the endometrium, choriodecidua and the fetal part of the placenta indicates local renin synthesis. Angiotensin (Ang) II, formed by the enzymatic action of tissue renin and Ang I converting enzyme, acts by interaction with its receptors. These receptors have been demonstrated in high densities in the placenta and uterus, indicating an autocrine or paracrine action of Ang II. Several probable effects of the uteroplacental RAS can be defined. It is very likely that the uteroplacental RAS plays an important role during implantation and placentation by stimulation of decidualization and angiogenesis. Furthermore, Ang II may regulate synthesis and secretion of other hormones formed locally in the uteroplacental unit. During labour the action of Ang II may be important for contraction of the uterine musculature, Ang II is also involved in the complex regulation of the uteroplacental blood flow. Species difference in the expression of the uteroplacental RAS exists, and one may speculate that the physiological and pathophysiological roles vary between species.

The midgestational maternal blood pressure decline is absent in mice lacking expression of the angiotensin II AT2 receptor

“…Indeed, all components of the RAS have been detected in the placenta, and the intra-placental RAS has been proposed to play an important role in regulating utero-placental blood flow. [13][14][15] Further to this, studies with AT1a-deficient mice demonstrate that this receptor is essential for normal placental functioning. 16 To our knowledge, few comprehensive quantitative ontogenic studies of change in placental Ang II receptor expression have been performed.…”

Expression of the Renin-Angiotensin System in a Human Placental Cell Line

“…[1][2][3][4][5][6] AGT has been detected in human placenta. 13,14 While some AGT may be taken up from the maternal or fetal circulation, studies using PCR amplification have demonstrated AGT mRNA in the human placenta indicating local expression.…”

“…The presence of a local RAS has been demonstrated in several tissues, including human placenta. [1][2][3][4][5][6] There is significant evidence to suggest that the local RAS in the placenta is involved in physiologic and pathophysiologic processes during pregnancy. 7,8 Ang II is involved in the regulation of uteroplacental vascular resistance and blood flow.…”

Angiotensin II mimics the hypoxic effect on regulating trophoblast proliferation and differentiation in human placental explant cultures

“…Angiotensin II (Ang II) is a most potent active peptide in the renin-angiotensin system (RAS). Recent studies showed that the feto-placental unit in pregnant women possesses all the components of the RAS including renin, angiotensinogen, angiotensin-converting enzyme (ACE) and angiotensin receptors (Lenz et al, 1989;Hagemann et al, 1994;Yagami et al, 1994;Nielsen et al, 2000), suggesting possible local production of Ang II and its involvement in physiological and pathological conditions of placenta. As cytokines and growth factors produced locally in placentas are known to affect diverse properties of trophoblasts such as cell differentiation and hormone production, it is hypothesized that locally produced Ang II may also have a significant effect on the differentiation of trophoblasts and developing preeclampsia.…”