Cardiovascular Research Advance Access originally published online on November 21, 2007
Cardiovascular Research 2008 77(3):452-462; doi:10.1093/cvr/cvm078
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Cardiac 
1-adrenergic drive in pathological remodelling
1 Cellular Biochemistry, Baker Heart Research Institute, Melbourne, Victoria 3004, Australia
2 Experimental Cardiology Laboratories, Baker Heart Research Institute, Melbourne, Victoria 3004, Australia
3 Molecular Cardiology and Biophysics Program, Victor Chang Cardiac Research Institute, Sydney, New South Wales 2010, Australia
4 University of New South Wales, Kensington, New South Wales 2033, Australia
* Corresponding author. Tel: +61 2 9295 8502; fax: +61 2 9295 8501. E-mail address: b.graham{at}victorchang.edu.au
The heart is richly innervated by sympathetic nerves, and both acute and chronic regulation of cardiac function via sympathetically released catecholamines acting on cardiomyocyte adrenergic receptors (ARs), is critical for circulatory homeostasis. Cardiomyocytes express 
1A- and 1B-, and β1- and β2-AR subtypes, which are all members of the G-protein-coupled receptor superfamily that signal via interaction with heterotrimeric G-proteins. Cardiac function – both inotropy and chronotropy – is regulated predominantly by β1-AR. Activation of 1-ARs also results in increased contractility, as well as changes in the electrophysiological properties and metabolic responses of the heart. Nonetheless, there is little evidence that cardiac 1-ARs play a major functional role under normal physiological conditions. In pathological settings, 1-ARs may function in a compensatory fashion to maintain cardiac inotropy when the β-AR system is downregulated and uncoupled from G-proteins and effectors. In addition, as we consider here, recent evidence from clinical studies and from genetically engineered animal models indicates that 1-ARs are importantly involved in both developmental cardiomyocyte growth, as well as pathological hypertrophy. In the presence of pressure overload or with myocardial infarction, activation of 1-ARs, particularly the 1A-subtype, also appears to produce important pro-survival effects at the level of the cardiomyocyte, and to protect against maladaptive cardiac remodelling and decompensation to heart failure.
KEYWORDS Adrenergic; Remodelling; Transgenic; Knockout; Cardiac; Hypertrophy
Time for primary review: 29 days