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1 Department of Experimental Medicine, Human Physiology Unit, University of Pavia, 27100 Pavia,2 Department of Anatomy and Physiology, University of Padova, 35131 Padova,3 Department of Physiological and Pharmacological Cellular-Molecular Sciences, Pharmacology and Molecular Biotechnologies Unit, University of Pavia, 27100 Pavia,4 Hospital S. Biagio, Department of Pneumology, 15100 Alessandria, Italy
Beta-agonists and glucocorticoids are frequently coprescribed for chronic asthma treatment. In this study the effects of 4 week treatment with beta-agonist clenbuterol (CL) and glucocorticoid dexamethasone (DEX) on respiratory (diaphragm and parasternal) and limb (soleus and tibialis) muscles of the mouse were studied. Myosin heavy chain (MHC) distribution, fibres cross sectional area (CSA), glycolytic (phosphofructokinase, PFK; lactate dehydrogenase, LDH) and oxidative enzyme (citrate synthase, CS; cytochrome oxidase, COX) activities were determined. Muscle samples were obtained from four groups of adult C57/B16 mice: (1) Control (2) Mice receiving CL (CL, 1.5 mg kg–1 day–1 in drinking water) (3) Mice receiving DEX (DEX, 5.7 mg kg–1 day–1S.C.) (4) Mice receiving both treatments (DEX + CL). As a general rule, CL and DEX showed opposite effects on CSA, MHC distribution, glycolytic and mitochondrial enzyme activities: CL alone stimulated a slow-to-fast transition of MHCs, an increase of PFK and LDH and an increase of muscle weight and fibre CSA; DEX produced an opposite (fast-to-slow transition) change of MHC distribution, a decrease of muscle weight and fibre CSA and in some case an increase of CS. The response varied from muscle to muscle with mixed muscles, as soleus and diaphragm, being more responsive than fast muscles, as tibialis and parasternal. In combined treatments (DEX + CL), the changes induced by DEX or CL alone were generally minimized: in soleus, however, the effects of CL predominated over those of DEX, whereas in diaphragm DEX prevailed over CL. Taken together the results suggest that CL might counteract the unwanted effects on skeletal muscles of chronic treatment with glucocorticoids.
(Received 12 June 2003;
accepted after revision 16 October 2003)
Corresponding author M. Pellegrino: Department of Experimental Medicine, Section of Human Physiology, University of Pavia, Via Forlanini 6, 27100 Pavia, Italy. Email: map{at}unipv.it
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