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Here, we tested whether sustained \u03b2AR stimulation with isoproterenol (ISO, 30\u2009mg\/kg\/day, 3\u2009days) exacerbates LV remodeling in male mice with germline deletion of <jats:italic>Rgs2<\/jats:italic> and\/or <jats:italic>Rgs5<\/jats:italic>. <jats:italic>Rgs2 KO and Rgs2\/5<\/jats:italic> dbKO mice showed LV dilatation at baseline, which was unchanged by ISO. <jats:italic>Rgs2<\/jats:italic> or <jats:italic>Rgs5 deletion decreased Rgs1<\/jats:italic> expression, whereas <jats:italic>Rgs5<\/jats:italic> deletion increased <jats:italic>Rgs4<\/jats:italic> expression. ISO induced cardiac hypertrophy and interstitial fibrosis in <jats:italic>Rgs2\/5<\/jats:italic> dbKO mice without increasing cardiomyocyte size or LV dilation but increased expression of cardiac fetal gene <jats:italic>Nppa<\/jats:italic>, \u03b1\u2010actinin, and Ca<jats:sup>2+<\/jats:sup>\u2010\/calmodulin\u2010dependent kinase II. Single <jats:italic>Rgs2<\/jats:italic> and <jats:italic>Rgs5<\/jats:italic> KO mice had markedly increased CD45<jats:sup>+<\/jats:sup> cells, whereas tissue from <jats:italic>Rgs5<\/jats:italic> KO mice showed increased CD68<jats:sup>+<\/jats:sup> cells, as revealed by immunohistochemistry. The results together indicate that ventricular remodeling due to <jats:italic>Rgs2<\/jats:italic> and\/or <jats:italic>Rgs5<\/jats:italic> deletion is associated with augmented myocardial immune cell presence but is not exacerbated by sustained \u03b2AR stimulation.<\/jats:p>","DOI":"10.14814\/phy2.70178","type":"journal-article","created":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T03:40:01Z","timestamp":1735875601000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Germline deletion of <i>Rgs2<\/i> and\/or <i>Rgs5<\/i> in male mice does not exacerbate left ventricular remodeling induced by subchronic isoproterenol infusion"],"prefix":"10.14814","volume":"13","author":[{"given":"Shelby","family":"Dahlen","sequence":"first","affiliation":[{"name":"Department of Physiology &amp; Biophysics Case Western Reserve University School of Medicine  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ipsita","family":"Mohanty","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Physiology Drexel University College of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Biophysics Case Western Reserve University School of Medicine  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanjana","family":"Nallapaneni","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Biophysics Case Western Reserve University School of Medicine  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4581-7044","authenticated-orcid":false,"given":"Patrick","family":"Osei\u2010Owusu","sequence":"additional","affiliation":[{"name":"Department of Physiology &amp; Biophysics Case Western Reserve University School of Medicine  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,1,2]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vph.2015.05.008"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2011.01.012"},{"issue":"6","key":"e_1_2_10_4_1","first-page":"899","article-title":"RGS protein specificity towards Gq\u2010 and Gi\/o\u2010mediated ERK 1\/2 and Akt activation, in\u00a0vitro","volume":"40","author":"Anger T.","year":"2007","journal-title":"Journal of Biochemistry and Molecular Biology"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2007.09.005"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.82.4.1249"},{"issue":"7","key":"e_1_2_10_7_1","article-title":"Inflammatory forms of cardiomyocyte cell death in the rat model of isoprenaline\u2010induced takotsubo syndrome","volume":"11","author":"Borodzicz\u2010Jazdzyk S.","year":"2023","journal-title":"Biomedicine"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198207223070401"},{"issue":"2","key":"e_1_2_10_9_1","first-page":"99","article-title":"Decreased mortality with beta\u2010blockers in patients with heart failure and coexisting atrial fibrillation: An AF\u2010CHF substudy. 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