© 1998 by European Society of Cardiology
Copyright © 1998, European Society of Cardiology
Clenbuterol induces cardiac hypertrophy with normal functional, morphological and molecular features
aDivision of Cardiothoracic Surgery, National Heart and Lung Institute, Imperial College of Science, Technology and Medicine, London, UK
bCentre for Cardiopulmonary Biochemistry, University College London, Rayne Institute, London, UK
* Corresponding author, at: Department of Cardiac Surgery, Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK. Tel.: +44 171 3518533; Fax: +44 171 3763442.
Objective: Several pharmacological agents have been shown to produce ‘physiological’ or ‘pathological’ hypertrophy based on their functional characteristics. The aim of this study was to examine the features of cardiac hypertrophy induced by the selective β2-adrenergic agonist, clenbuterol. Methods: Cardiac hypertrophy was induced in 7-week-old Sprague-Dawley rats by daily injections of clenbuterol for 3 weeks. Thyroxine and isoproterenol were also used to produce cardiac hypertrophy to serve as positive controls for physiological and pathological hypertrophy, respectively. Left ventricular function was determined using an isolated rat heart preparation. Ventricular samples were used for morphological examination while interstitial collagen was measured using high-pressure liquid chromatography. Expression of sarcoplasmic reticulum Ca2+-ATPase2a (SERCA2a) and phospholamban (PLB) were measured by dot blot analysis. Results: Clenbuterol treatment induced 26% left ventricular hypertrophy. These hearts demonstrated normal systolic isovolumic parameters and diastolic (active relaxation and passive stiffness) function. In addition, left ventricular concentration of collagen and morphology was normal as were the expression of SERCA2a and PLB mRNA. Conclusion: These results suggest that clenbuterol-induced hypertrophy is ‘physiological’ in terms of its function, extracellular structure and gene expression.
KEYWORDS β2-adrenergic agonist; Hypertrophy; Rat, ventricle
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