{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T14:58:01Z","timestamp":1790261881038,"version":"4.1.0"},"reference-count":40,"publisher":"American Physiological Society","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2013,5,1]]},"abstract":"<jats:p>\n                    The importance of chronic stimulation of \u03b2-adrenoceptors in the development of cardiac dysfunction is the rationale for the use of \u03b2-blockers in the treatment of heart failure. Nebivolol is a third-generation \u03b2-blocker, which has further properties including stimulation of endothelial nitric oxide synthase and\/or \u03b2\n                    <jats:sub>3<\/jats:sub>\n                    -adrenoceptors. The aim of this study was to investigate whether nebivolol has additional effects on \u03b2-adrenoceptor-mediated functional responses along with morphologic and molecular determinants of cardiac hypertrophy compared with those of metoprolol, a selective \u03b2\n                    <jats:sub>1<\/jats:sub>\n                    -adrenoceptor blocker. Rats infused by isoprenaline (100 \u03bcg\u00b7kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    \u00b7day\n                    <jats:sup>\u22121<\/jats:sup>\n                    , 14 days) were randomized into three groups according to the treatment with metoprolol (30 mg\u00b7kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    \u00b7day\n                    <jats:sup>\u22121<\/jats:sup>\n                    ), nebivolol (10 mg\u00b7kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    \u00b7day\n                    <jats:sup>\u22121<\/jats:sup>\n                    ), or placebo for 13 days starting on day 1 after implantation of minipump. Both metoprolol and nebivolol caused a similar reduction on heart rate. Nebivolol mediated a significant improvement on cardiac mass, coronary flow, mRNA expression levels of sarcoplasmic reticulum Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ATPase (SERCA2a) and atrial natriuretic peptide and phospholamban (PLN)\/SERCA2a and phospho-PLN\/PLN ratio compared with metoprolol and placebo. Nebivolol prevented the detrimental effects of isoprenaline infusion on isoprenaline (68% of control at 30 \u03bcM), BRL37344 (63% of control at 0.1 \u03bcM), and forskolin (64% of control at 1 \u03bcM) responses compared with metoprolol (isoprenaline, 34% of control; BRL37344, no response; forskolin, 26% of control) and placebo (isoprenaline, 33% of control; BRL37344, 28% of control; forskolin, 12% of control). Both \u03b2-blockers improved the changes in mRNA expressions of \u03b2\n                    <jats:sub>1<\/jats:sub>\n                    - and \u03b2\n                    <jats:sub>3<\/jats:sub>\n                    -adrenoceptors. Our results suggest that nebivolol partially protects the responsiveness of \u03b2-adrenoceptor signaling and the development of cardiac hypertrophy independent of its \u03b2\n                    <jats:sub>1<\/jats:sub>\n                    -adrenoceptor blocking effect.\n                  <\/jats:p>","DOI":"10.1152\/ajpheart.00352.2012","type":"journal-article","created":{"date-parts":[[2013,3,2]],"date-time":"2013-03-02T05:20:47Z","timestamp":1362201647000},"page":"H1267-H1276","source":"Crossref","is-referenced-by-count":19,"title":["Nebivolol prevents desensitization of \u03b2-adrenoceptor signaling and induction of cardiac hypertrophy in response to isoprenaline beyond \u03b2\n                    <sub>1<\/sub>\n                    -adrenoceptor blockage"],"prefix":"10.1152","volume":"304","author":[{"given":"Isil","family":"Ozakca","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, Ankara University, Ankara, Turkey; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ebru","family":"Arioglu-Inan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, Ankara University, Ankara, Turkey; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hrag","family":"Esfahani","sequence":"additional","affiliation":[{"name":"Pole of Pharmacology and Therapeutics, FATH\/IREC, Universite Catholique de Louvain, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V. Melih","family":"Altan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, Ankara University, Ankara, Turkey; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Luc","family":"Balligand","sequence":"additional","affiliation":[{"name":"Pole of Pharmacology and Therapeutics, FATH\/IREC, Universite Catholique de Louvain, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gizem","family":"Kayki-Mutlu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, Ankara University, Ankara, Turkey; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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