{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T02:58:23Z","timestamp":1790737103783,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,3,8]],"date-time":"2016-03-08T00:00:00Z","timestamp":1457395200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["AHA #09SDG2010138"],"award-info":[{"award-number":["AHA #09SDG2010138"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2016,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The known angiotensin II (AngII) physiological effect of aldosterone synthesis and secretion induction, a steroid hormone that contributes to the pathology of postmyocardial infarction (MI) heart failure (HF), is mediated by both G<jats:sub>q\/11<\/jats:sub>proteins and<jats:italic>\u03b2<\/jats:italic>\u2010arrestins, both of which couple to the AngII type 1 receptors (AT<jats:sub>1<\/jats:sub>Rs) of adrenocortical zona glomerulosa (AZG) cells. Over the past several years, AngII analogs with increased selectivity (\u201cbias\u201d) toward<jats:italic>\u03b2<\/jats:italic>\u2010arrestin\u2010dependent signaling at the AT<jats:sub>1<\/jats:sub>R have been designed and described, starting with SII, the gold\u2010standard<jats:italic>\u03b2<\/jats:italic>\u2010arrestin\u2010\u201dbiased\u201d AngII analog. In this study, we examined the relative potencies of an extensive series of AngII peptide analogs at relative activation of G proteins versus<jats:italic>\u03b2<\/jats:italic>\u2010arrestins by the AT<jats:sub>1<\/jats:sub>R. The major structural difference of these peptides from SII was their varied substitutions at position 5, rather than position 4 of native AngII. Three of them were found biased for<jats:italic>\u03b2<\/jats:italic>\u2010arrestin activation and extremely potent at stimulating aldosterone secretion in AZG cells in\u00a0vitro, much more potent than SII in that regard. Finally, the most potent of these three ([Sar<jats:sup>1<\/jats:sup>, Cys(Et)<jats:sup>5<\/jats:sup>, Leu<jats:sup>8<\/jats:sup>]\u2010AngII, CORET) was further examined in post\u2010MI rats progressing to HF and overexpressing adrenal<jats:italic>\u03b2<\/jats:italic>\u2010arrestin1 in\u00a0vivo. Consistent with the in\u00a0vitro studies, CORET was found to exacerbate the post\u2010MI hyperaldosteronism, and, consequently, cardiac function of the post\u2010MI animals in\u00a0vivo. Finally, our data suggest that increasing the size of position 5 of the AngII peptide sequence results in directly proportional increases in AT<jats:sub>1<\/jats:sub>R\u2010dependent<jats:italic>\u03b2<\/jats:italic>\u2010arrestin activation. These findings provide important insights for AT<jats:sub>1<\/jats:sub>R pharmacology and future AngII\u2010targeted drug development.<\/jats:p>","DOI":"10.1002\/prp2.226","type":"journal-article","created":{"date-parts":[[2016,3,10]],"date-time":"2016-03-10T16:48:44Z","timestamp":1457628524000},"source":"Crossref","is-referenced-by-count":29,"title":["Structure\u2013activity relationship study of angiotensin II analogs in terms of<i>\u03b2<\/i>\u2010arrestin\u2010dependent signaling to aldosterone production"],"prefix":"10.1002","volume":"4","author":[{"given":"Thairy Reyes","family":"Valero","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences Laboratory for the Study of Neurohormonal Control of the Circulation Nova Southeastern University College of Pharmacy Fort Lauderdale Florida 33328"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Sturchler","sequence":"additional","affiliation":[{"name":"Translational Research Institute Scripps Florida Jupiter Florida 33458"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malika","family":"Jafferjee","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Laboratory for the Study of Neurohormonal Control of the Circulation Nova Southeastern University College of Pharmacy Fort Lauderdale Florida 33328"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Rengo","sequence":"additional","affiliation":[{"name":"Salvatore Maugeri Foundation\u2013Scientific Institute of Telese Terme Telese Terme Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vassiliki","family":"Magafa","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Laboratory of Pharmacognosy &amp; Chemistry of Natural Products University of Patras Patras Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Cordopatis","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Laboratory of Pharmacognosy &amp; Chemistry of Natural Products University of Patras Patras Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"McDonald","sequence":"additional","affiliation":[{"name":"Translational Research Institute Scripps Florida Jupiter Florida 33458"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter J.","family":"Koch","sequence":"additional","affiliation":[{"name":"Center for Translational Medicine Temple University Philadelphia Pennsylvania 19140"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9817-6319","authenticated-orcid":false,"given":"Anastasios","family":"Lymperopoulos","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Laboratory for the Study of Neurohormonal Control of the Circulation Nova Southeastern University College of Pharmacy Fort Lauderdale Florida 33328"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,3,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1530\/JME-14-0125"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.113.02043"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncpneph0575"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep08116"},{"key":"e_1_2_8_6_1","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/S0031-6997(24)01458-3","article-title":"International union of pharmacology. 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