K Wong1, K R Boheler, J Bishop, M Petrou, M H Yacoub. 1. Division of Cardiothoracic Surgery, National Heart and Lung Institute, Imperial College of Science, Technology and Medicine, London, UK.
Abstract
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 beta 2-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 Ca(2+)-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.
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 beta 2-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 Ca(2+)-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.
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