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Antihypertensive drug classes differentially modulate this cascade. This study examined how four mechanistically distinct antihypertensive drugs affect plasma concentrations of 10 Ang peptides and aldosterone in untreated hypertensive patients. In this randomized, open-label, parallel-group study, 88 patients received 4 weeks of monotherapy with angiotensin-converting enzyme inhibitor (ACEi), angiotensin receptor blocker (ARB), calcium channel blocker (CCB), or hydrochlorothiazide (HCT). Equilibrium concentrations of 10 Ang peptides and aldosterone were quantified by LC\u2013MS at baseline and after 4 weeks, both pre- and 4\u2009h post-dose; drug exposure was confirmed by measured drug concentrations. Seventy-two participants completed the 4-week treatment (ACEi\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200918, ARB\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200917, CCB\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200920, HCT\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200917). The most prominent effects were seen for Ang I, Ang II, and aldosterone and were reflected in biomarkers for plasma renin activity (PRA-Q; Ang I+Ang II), ACE activity (ACE-Q; Ang II\/Ang I), and the aldosterone\/Ang II ratio (AA2-R). Downstream peptides showed minimal or no changes. Relative to baseline, ACEi increased Ang I and reduced ACE-Q. ARB increased Ang I and Ang II and lowered AA2-R without altering ACE-Q. CCB and HCT produced only minor changes. ACE-Q\u2009&lt;\u20091.05 pM\/pM identified ACEi use, and AA2-R\u2009&lt;\u20090.85 pM\/pM as well as Ang II\u2009&gt;\u2009175 pM identified ARB use. RAS-targeted monotherapy produces distinct peptide-level signatures that can be captured by Ang-derived biomarkers, supporting their potential utility for monitoring drug intake in personalized hypertension management.\n                  <\/jats:p>","DOI":"10.1038\/s41371-026-01239-1","type":"journal-article","created":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T17:28:26Z","timestamp":1791826106000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Angiotensin peptide and aldosterone concentrations in response to four classes of blood\u2010pressure-lowering drugs in hypertensive patients: A randomized trial"],"prefix":"10.1038","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6502-7197","authenticated-orcid":false,"given":"Vera","family":"van der Velpen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3069-9639","authenticated-orcid":false,"given":"Franziska","family":"K\u00fcng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Villiger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marko","family":"Poglitsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Finch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urs","family":"Duthaler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5188-1723","authenticated-orcid":false,"given":"Annina S.","family":"Vischer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6373-9820","authenticated-orcid":false,"given":"Thilo","family":"Burkard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2239-1378","authenticated-orcid":false,"given":"Evangelia","family":"Liakoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Kr\u00e4henb\u00fchl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1846-8640","authenticated-orcid":false,"given":"Manuel","family":"Haschke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,12]]},"reference":[{"key":"1239_CR1","first-page":"e212","volume":"82","author":"Writing","year":"2025","unstructured":"Writing, Committee M, Jones DW, Ferdinand KC, Taler SJ, Johnson HM, Shimbo D, et al. 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RF serves as a scientific advisory board member for aTENSION.life. The other authors declare that there are no conflicts of interest regarding this work.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"The study was performed in accordance with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines. The local ethics committee (Ethikkommission Nordwest- und Zentralschweiz EKNZ) approved the study and it was registered at clinicaltrials.gov (NCT02449811),\n                      \n                      , first registered 15MAY2015.","order":2,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Ethics"}}]}}