{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T19:32:28Z","timestamp":1781119948536,"version":"3.54.1"},"reference-count":65,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior Brasil - CAPES","award":["Finance Code 001"],"award-info":[{"award-number":["Finance Code 001"]}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["306037\/2019-0 and 307935\/2023-0"],"award-info":[{"award-number":["306037\/2019-0 and 307935\/2023-0"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"publisher","award":["E-26\/202.572\/2019, E-13\/2023-APQ1210.313\/2024 and CNE E-26\/ 210.190\/2018"],"award-info":[{"award-number":["E-26\/202.572\/2019, E-13\/2023-APQ1210.313\/2024 and CNE E-26\/ 210.190\/2018"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006507","name":"Funda\u00e7\u00e3o Oswaldo Cruz","doi-asserted-by":"publisher","award":["Grant PAEF3-IOC\/Fiocruz"],"award-info":[{"award-number":["Grant PAEF3-IOC\/Fiocruz"]}],"id":[{"id":"10.13039\/501100006507","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    High blood pressure is one of the leading global causes of cardiovascular diseases. The chronic action of high concentrations of angiotensin II (Ang II) promotes arterial hypertension. Ang II acts via AT\n                    <jats:sub>1<\/jats:sub>\n                    and AT\n                    <jats:sub>2<\/jats:sub>\n                    receptors. Acting via AT\n                    <jats:sub>1<\/jats:sub>\n                    R, Ang II can induce the production of inflammatory cytokines and reactive oxygen species, promoting oxidative stress, which may influence cardiac electrical traits. In hypertensive patients, a dispersed QTc interval may predict cardiovascular events and mortality. Benznidazole (Bz), an antiprotozoal prodrug, also has immunomodulatory properties. Here, we tested the idea that in a model of Ang II-induced BP overload, cardiomyopathy will be associated with a prolonged QTc interval. Then, we investigated the effects of Bz therapy on BP overload, electrical changes, and oxidant\/antioxidant imbalance. C57BL\/6 mice were implanted with an osmotic minipump containing Ang II or saline as a control. At 7 days post-surgery (dps), Ang II infusion increased mean BP, which was sustained until 28 dps. Further, the Ang II-infused group had prolonged QTc interval and QRS complex. Bz or the AT\n                    <jats:sub>1<\/jats:sub>\n                    R antagonist losartan (Los) were administered from 7 to 28 dps. Compared with the vehicle-treated group, Los therapy restored mean BP to normal but did not affect long-QTc. At 14 and 28 dps, Bz therapy improved BP, and restored QTc dispersion to normal, while improving RR interval and QRS complex changes. Ang II infusion increased IL-6 concentrations and oxidant\/antioxidant imbalance in cardiac tissue. Bz therapy showed a beneficial effect, tending to restore the IL-6 concentrations and oxidant\/antioxidant balance to physiological levels, which was correlated with reversal of the dispersed QTc interval. Altogether, our data support that Bz therapy deserves further evaluation as an anti-inflammatory and antioxidant adjuvant tool to improve BP overload and long-QTc syndrome underlying cardiovascular diseases.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0340280","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T18:40:51Z","timestamp":1769539251000},"page":"e0340280","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Benznidazole therapy improves pressure overload and cardiac electrical profile in an experimental model of Angiotensin II infusion-induced hypertension: Mechanistic insights"],"prefix":"10.1371","volume":"21","author":[{"given":"Ana Paula","family":"da Silva Pinheiro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glaucia","family":"Vilar-Pereira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leda","family":"Casta\u00f1o-Barrios","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isalira","family":"Peroba Rezende Ramos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmin","family":"Pedra-Rezende","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiza","family":"Dantas-Pereira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rubem","family":"Figueiredo Sadok Menna-Barreto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Gibaldi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilton Ant\u00f4nio","family":"Mata-Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5503-6754","authenticated-orcid":true,"given":"Joseli","family":"Lannes-Vieira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,1,27]]},"reference":[{"key":"pone.0340280.ref001","volume-title":"Hypertension [Internet","author":"World Health Organization","year":"2025"},{"issue":"3","key":"pone.0340280.ref002","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1161\/HYPERTENSIONAHA.118.11125","article-title":"Myocardial remodeling in hypertension: Toward a new view of hypertensive heart disease","volume":"72","author":"A Gonz\u00e1lez","year":"2018","journal-title":"Hypertension"},{"issue":"2","key":"pone.0340280.ref003","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1053\/eupc.2002.0227","article-title":"Hypertension and arrhythmia: blood pressure control and beyond","volume":"4","author":"A Yildirir","year":"2002","journal-title":"Europace"},{"issue":"5","key":"pone.0340280.ref004","article-title":"The renin-angiotensin system: going beyond the classical paradigms","volume":"316","author":"RAS Santos","year":"2019","journal-title":"Am J Physiol Heart Circ Physiol"},{"issue":"1","key":"pone.0340280.ref005","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.kisu.2021.11.002","article-title":"The renin-angiotensin system biomolecular cascade: a 2022 update of newer insights and concepts","volume":"12","author":"CM Ferrario","year":"2022","journal-title":"Kidney Int Suppl (2011)"},{"issue":"2","key":"pone.0340280.ref006","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/s13181-022-00885-4","article-title":"The Role of Angiotensin II in Poisoning-Induced Shock-a Review","volume":"18","author":"A Chen","year":"2022","journal-title":"J Med Toxicol"},{"issue":"4","key":"pone.0340280.ref007","doi-asserted-by":"crossref","first-page":"153","DOI":"10.3892\/etm.2023.11852","article-title":"Role of arterial hypertension and angiotensin II in chronic kidney disease (Review)","volume":"25","author":"MA Maranduca","year":"2023","journal-title":"Exp Ther Med"},{"issue":"9","key":"pone.0340280.ref008","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1590\/S0100-879X2002000900001","article-title":"Recent advances in angiotensin II signaling","volume":"35","author":"RM Touyz","year":"2002","journal-title":"Braz J Med Biol Res"},{"key":"pone.0340280.ref009","doi-asserted-by":"crossref","first-page":"112309","DOI":"10.1016\/j.mce.2024.112309","article-title":"Angiotensin II: Role in oxidative stress, endothelial dysfunction, and diseases","volume":"592","author":"A Ajoolabady","year":"2024","journal-title":"Mol Cell Endocrinol"},{"issue":"2","key":"pone.0340280.ref010","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1093\/europace\/eum283","article-title":"Electrophysiological effects of angiotensin II. 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