BENEFICIAL VERSUS ADVERSE-EFFECTS OF LONG-TERM USE OF CLENBUTEROL IN MDX MICE

Long-term administration of the beta(2)-adrenergic agonist clenbuterol in mdx mice was used to test the hypothesis that increasing contracti le protein content in skeletal muscle will decrease the progression of muscular dystrophy, C57BL/10SNJ (control) and dystrophic (mdx) mice w ere given clenbuterol (1.0-1.5 mg/kg body weight/day) in the drinking water, Ventilatory function and morphological and functional character istics of soleus (SOL) and diaphragm (DIA) muscles were evaluated, Cle nbuterol administration was associated with increased SOL muscle weigh t, and SOL muscle weight to body weight ratio in control and mdx mice at both ages, There was a 22% increase in myosin concentration of mdx DIA at 1 year of age, correlating well with increased normalized activ e tension in mdx DIA at this age, Also, absolute tetanic tension incre ased in control and mdx SOL with clenbuterol at both ages, Ventilatory function was significantly impaired in mdx mice at both ages and clen buterol administration did not alleviate this, Clenbuterol treatment w as associated with a 30-40% increase in fatigability in DIA and SOL mu scles of control and mdx mice at both ages, Furthermore, 1-year-old md x mice receiving clenbuterol exhibited deformities in hindlimbs and sp ine, These results suggest that long-term clenbuterol treatment has a positive effect on muscle growth and force generation, but has adverse side effects such as increased muscle fatigability and development of deformities, (C) 1995 John Wiley & Sons, Inc.