{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T10:38:48Z","timestamp":1792579128869,"version":"4.5.0"},"reference-count":55,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"National Institutes of Health","award":["T32HG008958"],"award-info":[{"award-number":["T32HG008958"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Cardiovasc Pharmacol Ther"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Pulmonary hypertension (PH) commonly complicates heart failure with preserved ejection fraction (HFpEF), driving morbidity and mortality, yet no therapies exist for HFpEF-PH. \u03b23-adrenergic receptor (ADRB3) agonists may provide cardiometabolic and anti-inflammatory benefits. We evaluated pharmacological ADRB3 modulation in a preclinical HFpEF-PH model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      HFpEF-PH was induced in male and female AKR\/J mice via high-fat diet feeding for 16-20 weeks. At 12-16 weeks of feeding, mice were randomized to low-dose mirabegron (LDM, 3.6 mg\/kg\/day), high-dose mirabegron (HDM, 14.4 mg\/kg\/day), nebivolol (1.0 mg\/kg\/day), or vehicle for 4 weeks. A separate cohort received the ADRB3 antagonist SR59230A (0.5 mg\/kg\/day) or vehicle. Right ventricular systolic pressure (RVSP), left ventricular end-diastolic pressure (LVEDP), body weight change, and gene expression of nitric oxide synthases (\n                      <jats:italic toggle=\"yes\">Nos1<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Nos2<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Nos3<\/jats:italic>\n                      ), thermogenic markers (\n                      <jats:italic toggle=\"yes\">Ucp1<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Ppargc1a<\/jats:italic>\n                      ), and inflammatory cytokines (\n                      <jats:italic toggle=\"yes\">Il1b<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Il6<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Tnf<\/jats:italic>\n                      ) were assessed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      HDM and nebivolol significantly reduced RVSP compared to controls (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.010 and\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =1.0\u00d710\n                      <jats:sup>-4<\/jats:sup>\n                      ), whereas SR59230A increased RVSP (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.006). LDM did not significantly affect RVSP, and LVEDP was unchanged across all treatment groups. HDM also reduced weight gain vs. control (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.023). HDM increased\n                      <jats:italic toggle=\"yes\">Ucp1<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Ppargc1a<\/jats:italic>\n                      expression in adipose tissue, and nebivolol increased\n                      <jats:italic toggle=\"yes\">Ppargc1a<\/jats:italic>\n                      expression in adipose tissue. These molecular findings remained significant in sensitivity analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>HDM and nebivolol reduced RVSP in a preclinical model of HFpEF-PH, whereas ADRB3 antagonism increased RVSP. These findings provide pharmacological evidence consistent with involvement of ADRB3 signaling and support further investigation of ADRB3-targeted approaches; the molecular pathways underlying these hemodynamic effects remain to be established.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/10742484261495417","type":"journal-article","created":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T14:06:16Z","timestamp":1792332376000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["\u03b23-Adrenergic Receptor Agonism Reduces Right Ventricular Systolic Pressure in a Preclinical Model of Heart Failure With Preserved Ejection Fraction-Associated Pulmonary Hypertension"],"prefix":"10.1177","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0468-8936","authenticated-orcid":false,"given":"Christelle","family":"Lteif","sequence":"first","affiliation":[{"name":"University of Florida College of Pharmacy"},{"name":"University of Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian E.","family":"Gawronski","sequence":"additional","affiliation":[{"name":"University of Florida College of Pharmacy"},{"name":"University of Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rylie M.","family":"Flohr","sequence":"additional","affiliation":[{"name":"University of Florida College of Pharmacy"},{"name":"University of Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5951-0626","authenticated-orcid":false,"given":"Ryanne J.","family":"Mulligan","sequence":"additional","affiliation":[{"name":"University of Florida College of Pharmacy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace C.","family":"Hogan","sequence":"additional","affiliation":[{"name":"University of Florida College of Pharmacy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyse S.","family":"Gomez","sequence":"additional","affiliation":[{"name":"University of Florida College of Pharmacy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravindra K.","family":"Sharma","sequence":"additional","affiliation":[{"name":"University of Florida College of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio D.","family":"Duarte","sequence":"additional","affiliation":[{"name":"University of Florida College of Pharmacy"},{"name":"University of Florida"},{"name":"Division of Pharmacy Practice and Science, The Ohio State University College of Pharmacy, Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,10,18]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/clc.70197"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2020.06.069"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00068.2024"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1155\/2024\/2005589"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehx366"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells8040357"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2011.12.046"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2013.04.025"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI9323"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.139160"},{"key":"e_1_3_6_12_2","volume-title":"Northbrook, IL: Astellas Pharma US","author":"Mirabegron [package insert]","year":"2021","unstructured":"Mirabegron [package insert]. Northbrook, IL: Astellas Pharma US. Inc.; 2021."},{"key":"e_1_3_6_13_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2023.3003"},{"key":"e_1_3_6_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.2745"},{"key":"e_1_3_6_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-015-0435-5"},{"key":"e_1_3_6_16_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2016-0177OC"},{"key":"e_1_3_6_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-55700-y"},{"key":"e_1_3_6_18_2","unstructured":"Nebivolol [package insert]. Madison NJ: Allergan USA: Inc.; 2023."},{"key":"e_1_3_6_19_2","volume-title":"Guidance for Industry: Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers","author":"U.S. Food and Drug Administration","year":"2005","unstructured":"U.S. Food and Drug Administration. Guidance for Industry: Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers. Center for Drug Evaluation and Research (CDER); 2005."},{"key":"e_1_3_6_20_2","doi-asserted-by":"publisher","DOI":"10.1177\/0091270007310378"},{"key":"e_1_3_6_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2009.00186.x"},{"key":"e_1_3_6_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.118.10934"},{"issue":"1","key":"e_1_3_6_23_2","first-page":"26","article-title":"Effects of tribromoethanol anesthesia on echocardiographic assessment of left ventricular function in mice","volume":"51","author":"Kiatchoosakun S","year":"2001","unstructured":"Kiatchoosakun S, Kirkpatrick D, Hoit BD. Effects of tribromoethanol anesthesia on echocardiographic assessment of left ventricular function in mice. Comp Med. 2001;51(1):26-29.","journal-title":"Comp Med"},{"key":"e_1_3_6_24_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2001.281.5.H1938"},{"key":"e_1_3_6_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/ilar.53.1.70"},{"key":"e_1_3_6_26_2","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0000000000000569"},{"key":"e_1_3_6_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.73"},{"key":"e_1_3_6_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jesp.2013.03.013"},{"key":"e_1_3_6_29_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-016-0567-0"},{"key":"e_1_3_6_30_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.120.000140"},{"key":"e_1_3_6_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehab389"},{"key":"e_1_3_6_32_2","doi-asserted-by":"publisher","DOI":"10.1139\/cjpp-2015-0431"},{"key":"e_1_3_6_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2014.11.050"},{"key":"e_1_3_6_34_2","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2019.8236"},{"key":"e_1_3_6_35_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-023-03614-0"},{"key":"e_1_3_6_36_2","doi-asserted-by":"publisher","DOI":"10.1111\/dom.13516"},{"key":"e_1_3_6_37_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.121510"},{"key":"e_1_3_6_38_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2011.00085"},{"key":"e_1_3_6_39_2","doi-asserted-by":"publisher","DOI":"10.1152\/advan.00052.2006"},{"key":"e_1_3_6_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0092-8674(00)81410-5"},{"key":"e_1_3_6_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature00904"},{"key":"e_1_3_6_42_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.104.076901"},{"key":"e_1_3_6_43_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI131126"},{"key":"e_1_3_6_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2014.12.009"},{"key":"e_1_3_6_45_2","doi-asserted-by":"publisher","DOI":"10.1124\/molpharm.121.000328"},{"key":"e_1_3_6_46_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.652246"},{"key":"e_1_3_6_47_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00698.2015"},{"key":"e_1_3_6_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2016.136"},{"key":"e_1_3_6_49_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abl4024"},{"key":"e_1_3_6_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.111289"},{"key":"e_1_3_6_51_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI134892"},{"key":"e_1_3_6_52_2","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.15549"},{"key":"e_1_3_6_53_2","doi-asserted-by":"publisher","DOI":"10.1177\/1753944709104496"},{"key":"e_1_3_6_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vph.2012.02.004"},{"key":"e_1_3_6_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2013.12.013"},{"key":"e_1_3_6_56_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvm008"}],"container-title":["Journal of Cardiovascular Pharmacology and Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/10742484261495417","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/10742484261495417","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/10742484261495417","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T09:46:26Z","timestamp":1792575986000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/10742484261495417"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":55,"alternative-id":["10.1177\/10742484261495417"],"URL":"https:\/\/doi.org\/10.1177\/10742484261495417","relation":{},"ISSN":["1074-2484","1940-4034"],"issn-type":[{"value":"1074-2484","type":"print"},{"value":"1940-4034","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10]]},"article-number":"10742484261495417"}}