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This Article Full Text Full Text (PDF) All Versions of this Article: 91/6/1041    most recent expphysiol.2006.035014v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Burniston, J. G. Articles by Goldspink, D. F. Search for Related Content PubMed PubMed Citation Articles by Burniston, J. G. Articles by Goldspink, D. F. Related Collections Heart/Cardiac Muscle

¹ Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Webster Street, Liverpool L3 2ET, UK ² Academic Unit of Molecular Vascular Medicine, University of Leeds, Leeds LS2 9JT, UK

The ß₂-adrenoceptor (ß₂-AR) agonists clenbuterol and fenoterol have similar beneficial effects in animal models of heart failure. However, large doses of clenbuterol can induce cardiomyocyte death, and it is not known which of these agents has the most favourable therapeutic profile. We have investigated the cardiotoxicity of clenbuterol and fenoterol alongside that of isoprenaline, and compared their haemodynamic effects. Wistar rats (n = 6 per group) were subcutaneously injected with each ß-agonist (0.003–3 mmol kg^–1) or saline, and cardiomyocyte apoptosis was detected by caspase 3 immunohistochemistry. In a separate experiment, rats (n = 4) were given equivalent doses to those used in the myotoxicity studies, in a randomized cross-over design, and their blood pressure recorded via radiotelemetry. Injection of 0.3 mmol kg^–1 fenoterol or isoprenaline, but not clenbuterol, induced significant cardiomyocyte apoptosis (0.4 ± 0.05%; P < 0.05). At 3 mmol kg^–1, all agonists induced apoptosis (fenoterol, 1.1 ± 0.1%; isoprenaline, 0.9 ± 0.8%; and clenbuterol, 0.4 ± 0.07%; P < 0.05). ß₁-Adrenoceptor antagonism (10 mg kg^–1 bisoprolol) prevented 92% (P < 0.05) of apoptosis induced by all three agonists, but clenbuterol-induced apoptosis could also be prevented by 96% (P < 0.05) by ß₂-AR antagonism (10 mg kg^–1 ICI 118 551). Clenbuterol decreased diastolic (1.3- to 1.6-fold; P < 0.05) and systolic blood pressure (1.3-fold; P < 0.05), and doses > 0.3 mmol kg^–1 increased heart rate (1.4-fold; P < 0.05). Fenoterol increased heart rate (1.2- to 1.4-fold; P < 0.05), and doses > 0.3 mmol kg^–1 decreased diastolic blood pressure (1.3-fold; P < 0.05). In conclusion, the cardiotoxicity of fenoterol was similar to isoprenaline and greater than clenbuterol, and fenoterol had less desirable haemodynamic effects.

(Received 13 July 2006; accepted after revision 4 September 2006; first published online 14 September 2006)
Corresponding author J. G. Burniston: Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Webster Street, Liverpool L3 2ET, UK. Email: j.burniston{at}ljmu.ac.uk

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