Activation of the Renin–Angiotensin–Aldosterone System Is Attenuated in Hypertensive Compared with Normotensive Pregnancy

Robin Shoemaker, Marko Poglitsch, Hong Huang, Katherine Vignes, Aarthi Srinivasan, Cynthia Cockerham, Aric Schadler, John A. Bauer, John M. O’Brien

Research output: Contribution to journalArticlepeer-review


Hypertension during pregnancy increases the risk of adverse maternal and fetal outcomes, but the mechanisms of pregnancy hypertension are not precisely understood. Elevated plasma renin activity and aldosterone concentrations play an important role in the normal physiologic adaptation to pregnancy. These effectors are reduced in patients with pregnancy hypertension, creating an opportunity to define the features of the renin–angiotensin–aldosterone system (RAAS) that are characteristic of this disorder. In the current study, we used a novel LC-MS/MS-based methodology to develop comprehensive profiles of RAAS peptides and effectors over gestation in a cohort of 74 pregnant women followed prospectively for the development of gestational hypertension and pre-eclampsia (HYP, 27 patients) versus those remaining normotensive (NT, 47 patients). In NT pregnancy, the plasma renin activity surrogate, (PRA-S, calculated from the sum of Angiotensin I + Angiotensin II) and aldosterone concentrations significantly increased from the first to the third trimester, accompanied by a modest increase in the concentrations of angiotensin peptide metabolites. In contrast, in HYP pregnancies, PRA-S and angiotensin peptides were largely unchanged over gestation, and third-trimester aldosterone concentrations were significantly lower compared with those in NT pregnancies. The results indicated that the predominant features of pregnancies that develop HYP are stalled or waning activation of the RAAS in the second half of pregnancy (accompanied by unchanging levels of angiotensin peptides) and the attenuated secretion of aldosterone.

Original languageEnglish
Article number12728
JournalInternational Journal of Molecular Sciences
Issue number16
StatePublished - Aug 2023

Bibliographical note

Funding Information:
The work was supported in part by a grant from the Kentucky BIRCWH Program, NIDA 5 K12 DA 35150-9 (R.S.), and by the Kentucky Children’s Hospital Children’s Miracle Network Research Fund.

Publisher Copyright:
© 2023 by the authors.


  • aldosterone
  • angiotensin
  • biomarkers
  • mass spectrometry
  • maternal
  • pregnancy hypertension

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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