{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T06:32:47Z","timestamp":1791873167572,"version":"4.3.4"},"reference-count":41,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,3,3]],"date-time":"2021-03-03T00:00:00Z","timestamp":1614729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>(1) Background: Recently, influences of antihypertensive treatment on the renin\u2013angiotensin\u2013aldosterone system (RAAS) has gained attention, regarding a possible influence on inflammatory and anti-inflammatory pathways. We aimed to study the effects of newly initiated antihypertensive drugs on angiotensin (Ang) II and Ang (1\u20137) as representers of two counter-regulatory axes. (2) Methods: In this randomized, open-label trial investigating RAAS peptides after the initiation of perindopril, olmesartan, amlodipine, or hydrochlorothiazide, Ang II and Ang (1\u20137) equilibrium concentrations were measured at 8 a.m. and 12 a.m. at baseline and after four weeks of treatment. Eighty patients were randomized (1:1:1:1 fashion). (3) Results: Between the four substances, we found significant differences regarding the concentrations of Ang II (p &lt; 0.0005 for 8 a.m., 12 a.m.) and Ang (1\u20137) (p = 0.019 for 8 a.m., &lt;0.0005 for 12 a.m.) four weeks after treatment start. Ang II was decreased by perindopril (p = 0.002), and increased by olmesartan (p &lt; 0.0005), amlodipine (p = 0.012), and hydrochlorothiazide (p = 0.001). Ang (1\u20137) was increased by perindopril and olmesartan (p = 0.008\/0.002), but not measurably altered by amlodipine and hydrochlorothiazide (p = 0.317\/ 0.109). (4) Conclusion: The initiation of all first line antihypertensive treatments causes early and distinct alterations of equilibrium angiotensin levels. Given the additional AT1R blocking action of olmesartan, RAAS peptides shift upon initiation of perindopril and olmesartan appear to work in favor of the anti-inflammatory axis compared to amlodipine and hydrochlorothiazide.<\/jats:p>","DOI":"10.3390\/cells10030534","type":"journal-article","created":{"date-parts":[[2021,3,3]],"date-time":"2021-03-03T20:33:57Z","timestamp":1614803637000},"page":"534","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Influence of Antihypertensive Treatment on RAAS Peptides in Newly Diagnosed Hypertensive Patients"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5188-1723","authenticated-orcid":false,"given":"Annina S.","family":"Vischer","sequence":"first","affiliation":[{"name":"Hypertension Clinic, Medical Outpatient Department and Hypertension Clinic, ESH Hypertension Centre of Excellence, University Hospital Basel, 4031 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8209-4631","authenticated-orcid":false,"given":"Gabriela M.","family":"Kuster","sequence":"additional","affiliation":[{"name":"Clinic of Cardiology, University Hospital Basel, 4031 Basel, Switzerland"},{"name":"Department of Biomedicine, University Hospital Basel and University of Basel, 4031 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael","family":"Twerenbold","sequence":"additional","affiliation":[{"name":"Clinic of Cardiology, University Hospital Basel, 4031 Basel, Switzerland"},{"name":"Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, 4031 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Otmar","family":"Pfister","sequence":"additional","affiliation":[{"name":"Clinic of Cardiology, University Hospital Basel, 4031 Basel, Switzerland"},{"name":"Department of Biomedicine, University Hospital Basel and University of Basel, 4031 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1828-4879","authenticated-orcid":false,"given":"Qian","family":"Zhou","sequence":"additional","affiliation":[{"name":"Clinic of Cardiology, University Hospital Basel, 4031 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Villiger","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology &amp; Toxicology, University Hospital Basel, 4031 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marko","family":"Poglitsch","sequence":"additional","affiliation":[{"name":"Attoquant Diagnostics GmbH, 1110 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8347-4145","authenticated-orcid":false,"given":"Stephan","family":"Kr\u00e4henb\u00fchl","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology &amp; Toxicology, University Hospital Basel, 4031 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Mayr","sequence":"additional","affiliation":[{"name":"Hypertension Clinic, Medical Outpatient Department and Hypertension Clinic, ESH Hypertension Centre of Excellence, University Hospital Basel, 4031 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9240-6731","authenticated-orcid":false,"given":"Stefan","family":"Osswald","sequence":"additional","affiliation":[{"name":"Clinic of Cardiology, University Hospital Basel, 4031 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Haschke","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology &amp; Toxicology, University Hospital Basel, 4031 Basel, Switzerland"},{"name":"Division of Clinical Pharmacology &amp; Toxicology, University Hospital Bern, 3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6373-9820","authenticated-orcid":false,"given":"Thilo","family":"Burkard","sequence":"additional","affiliation":[{"name":"Hypertension Clinic, Medical Outpatient Department and Hypertension Clinic, ESH Hypertension Centre of Excellence, University Hospital Basel, 4031 Basel, Switzerland"},{"name":"Clinic of Cardiology, University Hospital Basel, 4031 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1161\/CIRCULATIONAHA.115.018912","article-title":"Global Disparities of Hypertension Prevalence and Control: A Systematic Analysis of Population-Based Studies From 90 Countries","volume":"134","author":"Mills","year":"2016","journal-title":"Circulation"},{"key":"ref_2","unstructured":"Sommerstein, R., and Gr\u00e4ni, C. (2020). Rapid Response: Re: Preventing a covid-19 pandemic: ACE inhibitors as a potential risk factor for fatal Covid-19. BMJ."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Kuster, G.M., Pfister, O., Burkard, T., Zhou, Q., Twerenbold, R., Haaf, P., Widmer, A.F., and Osswald, S. (2020). SARS-CoV2: Should inhibitors of the renin-angiotensin system be withdrawn in patients with COVID-19?. Eur. Heart J.","DOI":"10.1093\/eurheartj\/ehaa235"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Fang, L., Karakiulakis, G., and Roth, M. (2020). Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?. Lancet Respir. Med.","DOI":"10.1016\/S2213-2600(20)30116-8"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1161\/CIRCRESAHA.116.307708","article-title":"Role of the ACE2\/Angiotensin 1-7 Axis of the Renin-Angiotensin System in Heart Failure","volume":"118","author":"Patel","year":"2016","journal-title":"Circ. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.1093\/eurheartj\/eht151","article-title":"2013 ESH\/ESC guidelines for the management of arterial hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC)","volume":"34","author":"Mancia","year":"2013","journal-title":"Eur. Heart J."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Glinz, D., Bl\u00e4si, C., Villiger, A., Meienberg, A., Socrates, T., Pfister, O., Mayr, M., Haschke, M., Vischer, A.S., and Burkard, T. (2020). Hemodynamic profiles in treatment-naive arterial hypertension and their clinical implication for treatment choice: An exploratory post hoc analysis. J. Hypertens.","DOI":"10.1097\/01.hjh.0000572396.70393.d3"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.jacc.2016.11.064","article-title":"Roles of Angiotensin Peptides and Recombinant Human ACE2 in Heart Failure","volume":"69","author":"Basu","year":"2017","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1373\/clinchem.2017.278705","article-title":"Low- and High-renin Heart Failure Phenotypes with Clinical Implications","volume":"64","author":"Pavo","year":"2018","journal-title":"Clin. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1161\/HYPERTENSIONAHA.119.12786","article-title":"Angs (Angiotensins) of the Alternative Renin-Angiotensin System Predict Outcome in Patients With Heart Failure and Preserved Ejection Fraction","volume":"74","author":"Binder","year":"2019","journal-title":"Hypertension"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"S53","DOI":"10.1097\/00005344-198900000-00012","article-title":"Angiotensin converting enzyme inhibition: Discrepancy between antihypertensive effect and suppression of enzyme activity","volume":"14","author":"Waeber","year":"1989","journal-title":"J. Cardiovasc. Pharm."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1111\/j.1445-5994.1986.tb02014.x","article-title":"Effects of enalapril and hydrochlorothiazide on blood pressure, renin-angiotensin system, and atrial natriuretic factor in essential hypertension: A double blind factorial cross-over study","volume":"16","author":"Chalmers","year":"1986","journal-title":"Aust. N. Z. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1097\/00005344-199704000-00003","article-title":"SC-52458, an orally active angiotensin II-receptor antagonist: Inhibition of blood pressure response to angiotensin II challenges and pharmacokinetics in normal volunteers","volume":"29","author":"Hagmann","year":"1997","journal-title":"J. Cardiovasc. Pharm."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.jash.2007.10.005","article-title":"Differential effect of low dose thiazides on the Renin Angiotensin system in genetically hypertensive and normotensive rats","volume":"2","author":"Jessup","year":"2008","journal-title":"J. Am. Soc. Hypertens"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"434618","DOI":"10.1155\/2013\/434618","article-title":"The influence of long term hydrochlorothiazide administration on the relationship between renin-angiotensin-aldosterone system activity and plasma glucose in patients with hypertension","volume":"2013","author":"Xiao","year":"2013","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1111\/j.1365-2125.1981.tb01231.x","article-title":"Effect of chronic diuretic treatment on the plasma renin-angiotensin-aldosterone system in essential hypertension","volume":"12","author":"Lijnen","year":"1981","journal-title":"Br. J. Clin. Pharm."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1111\/j.1476-5381.1996.tb15735.x","article-title":"Effect of amlodipine on renin secretion and renin gene expression in rats","volume":"119","author":"Schricker","year":"1996","journal-title":"Br. J. Pharm."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1159\/000210396","article-title":"Different effects of L\/N-type and L-type calcium channel blockers on the renin-angiotensin-aldosterone system in SHR\/Izm","volume":"30","author":"Konda","year":"2009","journal-title":"Am. J. Nephrol"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1159\/000323969","article-title":"Effects of an N-type calcium antagonist on angiotensin II-renin feedback","volume":"33","author":"Aritomi","year":"2011","journal-title":"Am. J. Nephrol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2156","DOI":"10.1097\/HJH.0b013e32833d01dd","article-title":"A new-generation N\/L-type calcium channel blocker leads to less activation of the renin-angiotensin system compared with conventional L type calcium channel blocker","volume":"28","author":"Konoshita","year":"2010","journal-title":"J. Hypertens."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Hoffmann, M., Kleine-Weber, H., Schroeder, S., Kr\u00fcger, N., Herrler, T., Erichsen, S., Schiergens, T.S., Herrler, G., Wu, N.H., and Nitsche, A. (2020). SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell.","DOI":"10.1016\/j.cell.2020.02.052"},{"key":"ref_22","unstructured":"(2020, March 25). ESH Update on Covid-19. Available online: https:\/\/www.eshonline.org\/spotlights\/esh-stabtement-on-covid-19\/."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.cardfail.2020.04.013","article-title":"HFSA\/ACC\/AHA Statement Addresses Concerns Re: Using RAAS Antagonists in COVID-19","volume":"5","author":"Bozkurt","year":"2020","journal-title":"J. Card. Fail."},{"key":"ref_24","unstructured":"De Simone, G. (2020, March 25). Position Statement of the ESC Council on Hypertension on ACE-Inhibitors and Angiotensin Receptor Blockers. Available online: https:\/\/www.escardio.org\/Councils\/Council-on-Hypertension-(CHT)\/News\/position-statement-of-the-esc-council-on-hypertension-on-ace-inhibitors-and-ang."},{"key":"ref_25","unstructured":"(2020, March 25). A statement from the International Society of Hypertension on COVID-19. Available online: https:\/\/ish-world.com\/news\/a\/A-statement-from-the-International-Society-of-Hypertension-on-COVID-19\/."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/nature03712","article-title":"Angiotensin-converting enzyme 2 protects from severe acute lung failure","volume":"436","author":"Imai","year":"2005","journal-title":"Nature"},{"key":"ref_27","first-page":"L885","article-title":"Angiotensin II induces apoptosis in human and rat alveolar epithelial cells","volume":"276","author":"Wang","year":"1999","journal-title":"Am. J. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1002\/1097-4652(200011)185:2<253::AID-JCP10>3.0.CO;2-#","article-title":"Apoptosis of lung epithelial cells in response to TNF-alpha requires angiotensin II generation de novo","volume":"185","author":"Wang","year":"2000","journal-title":"J. Cell Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e334","DOI":"10.1097\/CCM.0b013e31828a6688","article-title":"Angiotensin-(1\u20137) protects from experimental acute lung injury","volume":"41","author":"Klein","year":"2013","journal-title":"Crit. Care Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1002\/emmm.201000080","article-title":"Angiotensin II revisited: New roles in inflammation, immunology and aging","volume":"2","author":"Benigni","year":"2010","journal-title":"Embo Mol. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1161\/CIRCRESAHA.114.303045","article-title":"Angiotensin II, from vasoconstrictor to growth factor: A paradigm shift","volume":"114","author":"Vukelic","year":"2014","journal-title":"Circ. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2739","DOI":"10.1093\/eurheartj\/ehr253","article-title":"Therapeutic perspectives in hypertension: Novel means for renin-angiotensin-aldosterone system modulation and emerging device-based approaches","volume":"32","author":"Unger","year":"2011","journal-title":"Eur. Heart J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1161\/HYPERTENSIONAHA.106.076216","article-title":"Emerging evidence for a functional angiotensin-converting enzyme 2-angiotensin-(1\u20137)-MAS receptor axis: More than regulation of blood pressure?","volume":"50","author":"Chappell","year":"2007","journal-title":"Hypertension"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1038\/nature00786","article-title":"Angiotensin-converting enzyme 2 is an essential regulator of heart function","volume":"417","author":"Crackower","year":"2002","journal-title":"Nature"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s40635-015-0044-3","article-title":"Angiotensin-(1\u20137) improves oxygenation, while reducing cellular infiltrate and fibrosis in experimental Acute Respiratory Distress Syndrome","volume":"3","author":"Zambelli","year":"2015","journal-title":"Intensive Care Med. Exp."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1097\/SHK.0b013e318189017a","article-title":"Losartan prevents sepsis-induced acute lung injury and decreases activation of nuclear factor kappaB and mitogen-activated protein kinases","volume":"31","author":"Shen","year":"2009","journal-title":"Shock"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1038\/nm1267","article-title":"A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury","volume":"11","author":"Kuba","year":"2005","journal-title":"Nat. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1136\/thx.2006.061945","article-title":"Role of the renin-angiotensin system in ventilator-induced lung injury: An in vivo study in a rat model","volume":"62","author":"Jerng","year":"2007","journal-title":"Thorax"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2098","DOI":"10.1152\/japplphysiol.00514.2006","article-title":"Angiotensin-converting enzyme inhibitor captopril attenuates ventilator-induced lung injury in rats","volume":"102","author":"Jiang","year":"2007","journal-title":"J. Appl. Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"r1","DOI":"10.1530\/VB-20-0014","article-title":"Aging- and gender-related modulation of RAAS: Potential implications in COVID-19 disease","volume":"3","author":"Monteonofrio","year":"2021","journal-title":"Vasc. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e29","DOI":"10.1161\/HYPERTENSIONAHA.120.16724","article-title":"Concerns on the Specificity of Commercial ELISAs for the Measurement of Angiotensin (1\u20137) and Angiotensin II in Human Plasma","volume":"77","author":"Chappell","year":"2021","journal-title":"Hypertension"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/3\/534\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:32:04Z","timestamp":1760160724000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/3\/534"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,3]]},"references-count":41,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["cells10030534"],"URL":"https:\/\/doi.org\/10.3390\/cells10030534","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,3]]}}}