{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T17:44:02Z","timestamp":1793727842330,"version":"4.6.1"},"reference-count":83,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2023,8,12]],"date-time":"2023-08-12T00:00:00Z","timestamp":1691798400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Kentucky BIRCWH Program","award":["NIDA 5 K12 DA 35150-9"],"award-info":[{"award-number":["NIDA 5 K12 DA 35150-9"]}]},{"name":"Kentucky Children\u2019s Hospital Children\u2019s Miracle Network Research Fund","award":["NIDA 5 K12 DA 35150-9"],"award-info":[{"award-number":["NIDA 5 K12 DA 35150-9"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2013angiotensin\u2013aldosterone 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.<\/jats:p>","DOI":"10.3390\/ijms241612728","type":"journal-article","created":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T10:13:57Z","timestamp":1692008037000},"page":"12728","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Activation of the Renin\u2013Angiotensin\u2013Aldosterone System Is Attenuated in Hypertensive Compared with Normotensive Pregnancy"],"prefix":"10.3390","volume":"24","author":[{"given":"Robin","family":"Shoemaker","sequence":"first","affiliation":[{"name":"Department of Dietetics and Human Nutrition, University of Kentucky, Lexington, KY 40506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marko","family":"Poglitsch","sequence":"additional","affiliation":[{"name":"Attoquant Diagnostics GmbH, 1110 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Kentucky, Lexington, KY 40536, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Vignes","sequence":"additional","affiliation":[{"name":"Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of Kentucky, Lexington, KY 40506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aarthi","family":"Srinivasan","sequence":"additional","affiliation":[{"name":"Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of Kentucky, Lexington, KY 40506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Cockerham","sequence":"additional","affiliation":[{"name":"Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of Kentucky, Lexington, KY 40506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aric","family":"Schadler","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Kentucky, Lexington, KY 40536, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Bauer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Kentucky, Lexington, KY 40536, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of Kentucky, Lexington, KY 40506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1111\/1471-0528.17038","article-title":"Trends and outcomes for deliveries with hypertensive disorders of pregnancy from 2000 to 2018: A repeated cross-sectional study","volume":"129","author":"Wen","year":"2022","journal-title":"BJOG"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e75","DOI":"10.1161\/HYP.0000000000000227","article-title":"Appraising the Preclinical Evidence of the Role of the Renin-Angiotensin-Aldosterone System in Antenatal Programming of Maternal and Offspring Cardiovascular Health Across the Life Course: Moving the Field Forward: A Scientific Statement From the American Heart Association","volume":"80","author":"Alexander","year":"2023","journal-title":"Hypertension"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1161\/CIRCULATIONAHA.113.003901","article-title":"Pregnancy complications and cardiovascular disease death: 50-year follow-up of the Child Health and Development Studies pregnancy cohort","volume":"132","author":"Cirillo","year":"2015","journal-title":"Circulation"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e013991","DOI":"10.1161\/JAHA.119.013991","article-title":"Future Cardiovascular Disease Risk for Women With Gestational Hypertension: A Systematic Review and Meta-Analysis","volume":"9","author":"Lo","year":"2020","journal-title":"J. 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