Abstract
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.
Document Type
Article
Publication Date
8-2023
Digital Object Identifier (DOI)
https://doi.org/10.3390/ijms241612728
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.
Repository Citation
Shoemaker, Robin C.; Poglitsch, Marko; Huang, Hong; Vignes, Katherine; Srinivasan, Aarthi; Cockerham-Morris, Cynthia; Schadler, Aric; Bauer, John Anthony; and O'Brien, John, "Activation of the Renin–Angiotensin–Aldosterone System Is Attenuated in Hypertensive Compared with Normotensive Pregnancy" (2023). UK CARES Faculty Publications. 64.
https://uknowledge.uky.edu/ukcares_facpub/64
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Notes/Citation Information
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).