{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T16:53:11Z","timestamp":1769273591206,"version":"3.49.0"},"reference-count":24,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,11,22]],"date-time":"2020-11-22T00:00:00Z","timestamp":1606003200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21AR063956"],"award-info":[{"award-number":["R21AR063956"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:p>Mechanical ventilation (MV) is a life\u2010saving intervention for many critically ill patients. Unfortunately, prolonged MV results in the rapid development of inspiratory muscle weakness due to diaphragmatic atrophy and contractile dysfunction (termed ventilator\u2010induced diaphragm dysfunction (VIDD)). Although VIDD is a major risk factor for problems in weaning patients from MV, a standard therapy to prevent VIDD does not exist. However, emerging evidence suggests that pharmacological blockade of angiotensin II type 1 receptors (AT1Rs) protects against VIDD. Nonetheless, the essential characteristics of AT1R blockers (ARBs) required to protect against VIDD remain unclear. To determine the traits of ARBs that are vital for protection against VIDD, we compared the efficacy of two clinically relevant ARBs, irbesartan and olmesartan; these ARBs differ in molecular structure and effects on AT1Rs. Specifically, olmesartan blocks both angiotensin II (AngII) binding and mechanical activation of AT1Rs, whereas irbesartan prevents only AngII binding to AT1Rs. Using a well\u2010established preclinical model of prolonged MV, we tested the hypothesis that compared with irbesartan, olmesartan provides greater protection against VIDD. Our results reveal that irbesartan does not protect against VIDD whereas olmesartan defends against both MV\u2010induced diaphragmatic atrophy and contractile dysfunction. These findings support the hypothesis that olmesartan is superior to irbesartan in protecting against VIDD and are consistent with the concept that blockade of mechanical activation of AT1Rs is a required property of ARBs to shield against VIDD. These important findings provide a foundation for future clinical trials to evaluate ARBs as a therapy to protect against VIDD.<\/jats:p>","DOI":"10.1111\/cts.12916","type":"journal-article","created":{"date-parts":[[2020,11,22]],"date-time":"2020-11-22T18:43:49Z","timestamp":1606070629000},"page":"481-486","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Comparative Efficacy of Angiotensin II Type 1 Receptor Blockers Against Ventilator\u2010Induced Diaphragm Dysfunction in Rats"],"prefix":"10.1111","volume":"14","author":[{"given":"Stephanie E.","family":"Hall","sequence":"first","affiliation":[{"name":"Department of Anatomy and Physiology Kansas State University Manhattan Kansas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bumsoo","family":"Ahn","sequence":"additional","affiliation":[{"name":"Aging and Metabolism Research Program Oklahoma Medical Research Foundation Oklahoma City Oklahoma USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashley J.","family":"Smuder","sequence":"additional","affiliation":[{"name":"Department of Applied Physiology and Kinesiology University of Florida Gainesville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aaron B.","family":"Morton","sequence":"additional","affiliation":[{"name":"University of Missouri Columbia Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. 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