{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:33:10Z","timestamp":1791232390231,"version":"4.1.0"},"reference-count":38,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2010,6]]},"abstract":"<jats:p> Exercise training has been reported to exert beneficial effects on cardiac function and to reduce morbidity and mortality of chronic heart failure (HF). Augmented sympathetic nervous system (SNS) activity, leading to elevated circulating catecholamine (CA) levels, is a hallmark of chronic HF that significantly aggravates this disease. Exercise training has been shown to also reduce SNS overactivity in HF, but the underlying molecular mechanism(s) remain unidentified. We recently reported that adrenal G protein-coupled receptor kinase-2 (GRK2), an enzyme that regulates the sympathoinhibitory \u03b1<jats:sub>2<\/jats:sub>-adrenoceptors (\u03b1<jats:sub>2<\/jats:sub>-ARs) present in the CA-producing adrenal medulla, is upregulated in HF, contributing to the chronically elevated CA levels and SNS activity of the disease. In the present study, we tested whether exercise training can affect the adrenal GRK2-\u03b1<jats:sub>2<\/jats:sub>-AR-CA production system in the context of HF. For this purpose, a 10-wk-long exercise training regimen of adult male Sprague-Dawley rats starting at 4 wk postmyocardial infarction (post-MI) was employed, and examination at the end of this treatment period revealed significant amelioration of \u03b2-AR-stimulated contractility in response to exercise training, accompanied by cardiac GRK2 reduction and restoration of circulating plasma CA levels. Importantly, adrenal GRK2 expression (72 \u00b1 5% reduction vs. post-MI untrained) and \u03b1<jats:sub>2<\/jats:sub>-AR number were also restored after exercise training in post-MI animals. These results suggest that exercise training restores the adrenal GRK2-\u03b1<jats:sub>2<\/jats:sub>-AR-CA production axis, and this might be part of the mechanism whereby this therapeutic modality normalizes sympathetic overdrive and impedes worsening of the failing heart. <\/jats:p>","DOI":"10.1152\/ajpheart.00702.2009","type":"journal-article","created":{"date-parts":[[2010,3,20]],"date-time":"2010-03-20T02:39:23Z","timestamp":1269052763000},"page":"H2032-H2038","source":"Crossref","is-referenced-by-count":56,"title":["Adrenal GRK2 lowering is an underlying mechanism for the beneficial sympathetic effects of exercise training in heart failure"],"prefix":"10.1152","volume":"298","author":[{"given":"Giuseppe","family":"Rengo","sequence":"first","affiliation":[{"name":"Cardiology Division, Fondazione \u201cSalvatore Maugeri,\u201d Istituto di Ricovero e Cura a Carattere Scientifico, Telese Terme (BN), Italy;"},{"name":"Center for Translational Medicine and the George Zallie and Family Laboratory for Cardiovascular Gene Therapy, Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dario","family":"Leosco","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Cardiovascular and Immunological Sciences, University \u201cFederico II,\u201d Naples;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmela","family":"Zincarelli","sequence":"additional","affiliation":[{"name":"Center for Translational Medicine and the George Zallie and Family Laboratory for Cardiovascular Gene Therapy, Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania;"},{"name":"Department of Internal Medicine, Cardiovascular and Immunological Sciences, University \u201cFederico II,\u201d Naples;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Marchese","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Cardiovascular and Immunological Sciences, University \u201cFederico II,\u201d Naples;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graziamaria","family":"Corbi","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University of Molise, Campobasso;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Liccardo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Cardiovascular and Immunological Sciences, University \u201cFederico II,\u201d Naples;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelia","family":"Filippelli","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine and Excellence Center of Cardiovascular Disease, Second University of Naples, Naples, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Ferrara","sequence":"additional","affiliation":[{"name":"Cardiology Division, Fondazione \u201cSalvatore Maugeri,\u201d Istituto di Ricovero e Cura a Carattere Scientifico, Telese Terme (BN), Italy;"},{"name":"Department of Health Sciences, University of Molise, Campobasso;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Lisanti","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter J.","family":"Koch","sequence":"additional","affiliation":[{"name":"Center for Translational Medicine and the George Zallie and Family Laboratory for Cardiovascular Gene Therapy, Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasios","family":"Lymperopoulos","sequence":"additional","affiliation":[{"name":"Center for Translational Medicine and the George Zallie and Family Laboratory for Cardiovascular Gene Therapy, Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania;"},{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Ft. 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