β-adrenoceptor agonist clenbuterol down-regulates matrix metalloproteinase (MMP-9) and results in an impairment of collagen turnover in mice left ventricle

An oral administration of a single dose of P-adrenoceptor agonist clenbuterol (15 mg/kg body weight) to mice resulted in an increased collagen distribution in the subendocardium and myocardium of the left ventricle. Abundant collagen accumulation is characteristic in myonecrotic regions and around blood vessels. Hydroxyproline assay and sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) of pepsin insoluble collagen confirmed this stimulated collagen proliferation. An MMP-activity assay of tissue extract by gelatin in gel zymography demonstrated a significant inhibition of MMP-9 activity in the P-agonist-treated group. The results suggest that clenbuterol treatment is capable of inducing structural and functional remodeling of the extracellular matrix by down-regulating MMP-9 activity and thereby causing an impairment of collagen turnover. This may lead to changes in the different hemodynamic properties of the tissue, including ventricular compliance.