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We aimed to characterize expression and function of adenosine A<jats:sub>1<\/jats:sub>receptors following hypertrophic stimulation<jats:italic>in vitro<\/jats:italic>and<jats:italic>in vivo<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Pro\u2010hypertrophic stimuli and adenosine A<jats:sub>1<\/jats:sub>receptor stimulation of neonatal rat cardiomyocytes and male C57\/Bl6 mice, sc. drug administration, real\u2010time PCR,<jats:sup>3<\/jats:sup>[H]\u2010leucine\u2010incorporation assay, immunostaining, tissue staining, Western blots, gravimetric analyses and echocardiography were applied in this study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>In neonatal rat cardiomyocyte cultures, phenylephrine, but not angiotensin II or insulin\u2010like growth factor 1 (IGF1), up\u2010regulated adenosine A<jats:sub>1<\/jats:sub>receptors concentration\u2010dependently. The hypertrophic phenotype (cardiomyocyte size, sarcomeric organization, total protein synthesis, c\u2010fos expression) mediated by phenylephrine (10\u2009\u03bcM), but not that by angiotensinII (1\u2009\u03bcM) or IGF1 (20\u2009ng\u00b7mL<jats:sup>\u22121<\/jats:sup>), was counteracted by the selective A<jats:sub>1<\/jats:sub>receptor agonist, N6\u2010cyclopentyladenosine. In C57\/BL6 mice, continuous N6\u2010cyclopentyladenosine infusion (2\u2009mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup>; 21\u2009days) blunted phenylephrine (120\u2009mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup>; 21\u2009days) induced hypertrophy (heart weight, cardiomyocyte size and fetal genes), fibrosis, MMP 2 up\u2010regulation and generation of oxidative stress \u2013 all hallmarks of maladaptive remodelling. Concurrently, phenylephrine administration increased expression of adenosine A<jats:sub>1<\/jats:sub>receptors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>We have presented evidence for a negative feedback mechanism attenuating pathological myocardial hypertrophy following<jats:italic><jats:bold>\u03b1<\/jats:bold><\/jats:italic><jats:sub>1<\/jats:sub>\u2010adrenoceptor stimulation. Our results suggest adenosine A<jats:sub>1<\/jats:sub>receptors as potential targets for therapeutic strategies to prevent transition from compensated myocardial hypertrophy to decompensated heart failure due to chronic cardiac pressure overload.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13339","type":"journal-article","created":{"date-parts":[[2015,9,25]],"date-time":"2015-09-25T17:32:58Z","timestamp":1443202378000},"page":"88-102","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Adenosine A<sub>1<\/sub>receptor activation attenuates cardiac hypertrophy and fibrosis in response to \u03b1<sub>1<\/sub>\u2010adrenoceptor stimulation<i>in vivo<\/i>"],"prefix":"10.1111","volume":"173","author":[{"given":"S\u2010L","family":"Puhl","sequence":"first","affiliation":[{"name":"Klinik f\u00fcr Innere Medizin III (Kardiologie, Angiologie, Internistische Intensivmedizin) Universit\u00e4tsklinikum des Saarlandes Homburg\/Saar 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