Renin-Angiotensin System Dynamics in Pregnancy

The renin–angiotensin system (RAS) orchestrates cardiovascular and fluid homeostasis through a cascade of peptide hormones and receptors. In pregnancy, adaptive up-regulation of renin release, angiotensin II (Ang II) generation and aldosterone synthesis supports the maternal plasma volume expansion and uteroplacental perfusion essential for foetal growth. Simultaneously, the counter-regulatory axis—comprising angiotensin-converting enzyme 2 (ACE2), angiotensin-(1-7) and the Mas receptor—promotes vasodilatation and anti-inflammatory effects within the uterine and placental vasculature. Proper balance between the vasoconstrictor Ang II–AT1 receptor pathway and the vasodilator Ang-(1-7)–Mas axis underpins normal gestational haemodynamics. Dysregulation of this interplay contributes to hypertensive disorders of pregnancy, notably pre-eclampsia and foetal growth restriction, through impaired blood-volume expansion, endothelial dysfunction and aberrant placental development. Emerging evidence also implicates local tissue RAS components within the decidua and foetal membranes as determinants of implantation success and vascular remodelling. A comprehensive understanding of systemic and intraplacental RAS dynamics illuminates potential biomarkers for early detection of complications and reveals therapeutic targets to rebalance vasoactive mediators in pathological pregnancies.

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Renin-Angiotensin System Dynamics in Pregnancy publication trend

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Technical terms

Renin: A kidney-derived enzyme that catalyses the conversion of angiotensinogen to angiotensin I, initiating RAS activation.

Angiotensin II (Ang II): A potent vasoconstrictor peptide that raises blood pressure and stimulates aldosterone release.

Angiotensin-(1-7) (Ang-(1-7)): A vasodilatory peptide formed by ACE2 that opposes Ang II actions via the Mas receptor.

ACE2: Angiotensin-converting enzyme 2, a monocarboxypeptidase that degrades Ang II to Ang-(1-7) and modulates RAS balance.

Mas receptor: A G-protein-coupled receptor activated by Ang-(1-7) to promote vasodilatation and anti-inflammatory signalling.

Aldosterone: A mineralocorticoid hormone that enhances renal sodium retention and plasma volume expansion in pregnancy.

References

1. Active plasma renin concentration throughout healthy and complicated pregnancy: a systematic review and meta-analysis. Reproductive Biology and Endocrinology (2024).
2. Activation of the Renin–Angiotensin–Aldosterone System Is Attenuated in Hypertensive Compared with Normotensive Pregnancy. International Journal of Molecular Sciences (2023).
3. G-protein-coupled receptor MAS deletion produces a preeclampsia-like phenotype in FVB/N mice. Clinical Science (2023).
4. Association of angiotensin II and receptors in peri-implantation endometrium with microvessel density and pregnancy outcomes of women with recurrent implantation failure after embryo transfer. Frontiers in Endocrinology (2023).