Clenbuterol reduces degeneration of exercised or aged dystrophic (mdx) muscle

Evidence of dystrophic muscle degeneration in the hind limb muscles of youn g (20-week-old) treadmill-exercised or aged (87-week-old) sedentary mdx mic e was greatly reduced by treatment with clenbuterol, a beta(2)-adrenoceptor agonist. Daily treadmill exercise for 10 weeks increased the size of regio ns within the mdx plantaris but not the soleus or gastrocnemius muscles, in which necrotic muscle fibers or the absence of fibers was observed. Clenbu terol reduced the size of these abnormal regions from 21% of total muscle c ross-sectional area to levels (4%) found in sedentary mdx mice. In addition , the muscles obtained from aged clenbuterol-treated mdx or wild-type mice did not display the extensive fibrosis or fiber loss observed in untreated mdx mice. These observations are consistent with a mechanism of dystrophic muscle degeneration caused by work load-induced injury that is cumulative w ith aging and is opposed by beta(2)-adrenoceptor activation. Optimization o f beta(2)-agonist treatment of muscular dystrophy in mdx mice may lead to a useful therapeutic modality for human forms of the disease. (C) 2000 John Wiley & Sons, Inc.