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While \u03b2<jats:sub>1H<\/jats:sub>\u2010adrenoceptor can be blocked by all clinically used \u03b2\u2010blockers, \u03b2<jats:sub>1L<\/jats:sub>\u2010adrenoceptor is relatively resistant to blockade. Thus, chronic \u03b2<jats:sub>1L<\/jats:sub>\u2010adrenoceptor activation may mediate persistent cardiostimulation, despite the concurrent blockade of \u03b2<jats:sub>1H<\/jats:sub>\u2010adrenoceptors. Hence, it is important to determine the potential significance of \u03b2<jats:sub>1L<\/jats:sub>\u2010adrenoceptors <jats:italic>in vivo<\/jats:italic>, particularly in pathological situations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">C57Bl<\/jats:styled-content>\/6 male mice were used. Chronic (4 or 8 weeks) \u03b2<jats:sub>1L<\/jats:sub>\u2010adrenoceptor activation was achieved by treatment, via osmotic mini pumps, with (\u2010)\u2010<jats:styled-content style=\"fixed-case\">CGP<\/jats:styled-content>12177 (10\u2009mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup>). Cardiac function was assessed by echocardiography and micromanometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>(\u2010)\u2010<jats:styled-content style=\"fixed-case\">CGP<\/jats:styled-content>12177 treatment of healthy mice increased heart rate and left ventricular (<jats:styled-content style=\"fixed-case\">LV<\/jats:styled-content>) contractility. (\u2010)\u2010<jats:styled-content style=\"fixed-case\">CGP<\/jats:styled-content>12177 treatment of mice subjected to transverse aorta constriction (<jats:styled-content style=\"fixed-case\">TAC<\/jats:styled-content>), during weeks 4\u20138 or 4\u201312 after <jats:styled-content style=\"fixed-case\">TAC<\/jats:styled-content>, led to a positive inotropic effect and exacerbated fibrogenic signalling while cardiac hypertrophy tended to be more severe. (\u2010)\u2010<jats:styled-content style=\"fixed-case\">CGP<\/jats:styled-content>12177 treatment of mice with <jats:styled-content style=\"fixed-case\">TAC<\/jats:styled-content> also exacerbated the myocardial expression of hypertrophic, fibrogenic and inflammatory genes compared to untreated TAC mice. Washout of (\u2010)\u2010<jats:styled-content style=\"fixed-case\">CGP<\/jats:styled-content>12177 revealed a more pronounced cardiac dysfunction after 12 weeks of <jats:styled-content style=\"fixed-case\">TAC<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>\u03b2<jats:sub>1L<\/jats:sub>\u2010adrenoceptor activation provides functional support to the heart, in both normal and pathological (pressure overload) situations. Sustained \u03b2<jats:sub>1L<\/jats:sub>\u2010adrenoceptor activation in the diseased heart exacerbates <jats:styled-content style=\"fixed-case\">LV<\/jats:styled-content> remodelling and therefore may promote disease progression from compensatory hypertrophy to heart failure.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.12272","type":"journal-article","created":{"date-parts":[[2013,6,11]],"date-time":"2013-06-11T11:35:32Z","timestamp":1370950532000},"page":"352-365","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Chronic activation of the low affinity site of \u03b2<sub>1<\/sub>\u2010adrenoceptors stimulates haemodynamics but exacerbates pressure\u2010overload cardiac remodelling"],"prefix":"10.1111","volume":"170","author":[{"given":"Helen","family":"Kiriazis","sequence":"first","affiliation":[{"name":"Experimental Cardiology Laboratory Baker IDI Heart and Diabetes Institute  Melbourne Vic. 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