CLENBUTEROL INDUCES CARDIAC-HYPERTROPHY WITH NORMAL FUNCTIONAL, MORPHOLOGICAL AND MOLECULAR-FEATURES

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 ago nist, 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 hypert rophy to serve as positive controls for physiological and pathological hypertrophy, respectively. Left ventricular function was determined u sing 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 measur ed by dot blot analysis. Results: Clenbuterol treatment induced 26% le ft ventricular hypertrophy. These hearts demonstrated normal systolic isovolumic parameters and diastolic (active relaxation and passive sti ffness) function, In addition, left ventricular concentration of colla gen and morphology was normal as were the expression of SERCA2a and PL B mRNA. Conclusion: These results suggest that clenbuterol-induced hyp ertrophy is 'physiological' in terms of its function, extracellular st ructure and gene expression. (C) 1998 Elsevier Science B.V.