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Longitudinal study of angiotensin peptides in normal and pre-eclamptic pregnancy

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Abstract

Purpose

To address whether differential regulation of the renin-angiotensin-aldosterone system occurs in pre-eclampsia, we performed an analysis of the time course of circulating and urinary profiles of the vasoconstrictor (Ang II) and the vasodilator [Ang-(1–7)] peptides in normal pregnant (NP) and pre-eclamptic (PE) women.

Methods

Urine and plasma samples from 86 nulliparous women were collected prospectively; 67 subjects continued as NP and 19 developed PE. Subjects were enrolled prior to 12 weeks of gestation and plasma and spot urine samples were obtained throughout gestation. Control samples were obtained at 6 weeks postpartum (PP).

Results

Mean blood pressure (p < 0.001) was elevated at 31–37 weeks of gestation in PE subjects as compared with NP subjects. Plasma Ang I and Ang II levels were elevated in NP subjects as early as 16 weeks of gestation and maintained throughout gestation. In PE subjects both plasma Ang I and Ang II were elevated at 16–33 weeks as compared with PP levels. PE subjects showed reduced plasma Ang I and Ang II (at 35–37 weeks of gestation) compared with NP subjects. Plasma Ang-(1–7) was unchanged in both groups. All three urinary peptides increased throughout gestation in NP subjects. In PE subjects urinary Ang I was increased at 23–26 weeks and was maintained throughout gestation. Urinary Ang II was increased at 27–29 and 31–33 weeks of gestation. PE subjects had no change in urinary Ang-(1–7).

Conclusion

The activation of the RAS, particularly Ang II throughout normal gestation may contribute to the maintenance of vascular tone during normal pregnancy. However higher sensitivity to Ang II in pre-eclampsia may be potentiated by the higher circulating and urinary levels of Ang II, unopposed by local renal Ang-(1–7), and thus may contribute to the development of pre-eclampsia.

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Acknowledgements

The authors gratefully acknowledge support in part provided by R. Odell Farley Research Fund in Hypertension and Vascular Disease. We acknowledge the contributions of the Biomarker Analytical Core of the Hypertension and Vascular Research Center.

Funding

This study was funded by NIH/NHLBI HL070130 (David C. Merrill, PI) and NICHD 42631 (K. Bridget Brosnihan, PI).

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Author notes

  1. These authors contributed equally: K. Bridget Brosnihan, David C. Merrill

Authors and Affiliations

  1. Department of Surgery/Hypertension and Vascular Research, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA

    K. Bridget Brosnihan, Liliya M. Yamaleyeva, Liomar Neves, JaNae Joyner, Courtney Givner, Kristy Lanier, Cheryl Moorefield & Brian Westwood

  2. Aspirus Wausau Medical Center, Wausau, WI, 54401, USA

    David C. Merrill & Kai Chen

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  1. K. Bridget Brosnihan
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Correspondence to K. Bridget Brosnihan.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Brosnihan, K.B., Merrill, D.C., Yamaleyeva, L.M. et al. Longitudinal study of angiotensin peptides in normal and pre-eclamptic pregnancy. Endocrine 69, 410–419 (2020). https://doi.org/10.1007/s12020-020-02296-3

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