Document Detail


Relative myotoxic and haemodynamic effects of the beta-agonists fenoterol and clenbuterol measured in conscious unrestrained rats.
MedLine Citation:
PMID:  16973691     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The beta(2)-adrenoceptor (beta(2)-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 beta-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). beta(1)-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 beta(2)-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.
Authors:
Jatin G Burniston; Lip-Bun Tan; David F Goldspink
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-09-14
Journal Detail:
Title:  Experimental physiology     Volume:  91     ISSN:  0958-0670     ISO Abbreviation:  Exp. Physiol.     Publication Date:  2006 Nov 
Date Detail:
Created Date:  2006-11-19     Completed Date:  2006-12-19     Revised Date:  2013-03-27    
Medline Journal Info:
Nlm Unique ID:  9002940     Medline TA:  Exp Physiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1041-9     Citation Subset:  IM    
Affiliation:
Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Webster Street, Liverpool L3 2ET, UK. j.burniston@ljmu.ac.uk
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MeSH Terms
Descriptor/Qualifier:
Adrenergic beta-Agonists / pharmacology,  toxicity*
Animals
Apoptosis / drug effects,  physiology
Blood Pressure / drug effects*,  physiology
Clenbuterol / pharmacology,  toxicity*
Dose-Response Relationship, Drug
Fenoterol / pharmacology,  toxicity*
Heart Rate / drug effects*,  physiology
Male
Muscle Cells / drug effects*,  physiology
Myocytes, Cardiac / drug effects
Rats
Rats, Wistar
Time Factors
Grant Support
ID/Acronym/Agency:
FS/04/028/16327//British Heart Foundation
Chemical
Reg. No./Substance:
0/Adrenergic beta-Agonists; 13392-18-2/Fenoterol; 37148-27-9/Clenbuterol
Comments/Corrections

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