ANABOLIC EFFECTS OF CLENBUTEROL AFTER LONG-TERM TREATMENT AND WITHDRAWAL IN THE RAT

Injection of rats with the beta(2)-adrenoceptor agonist clenbuterol (1 mg/kg/d for 15 days) stimulated an increase in body weight (9%) and protein (8%) and water (7%) content, but reduced food intake (4%) and epididymal fat pad mass (39%). Nine days after termination of treatment, ex-clenbuterol rats were heavier (5%) and had a greater protein (7%) and water (6%) content and lower fat pad mass (32%) than controls. Clenbuterol-fed rats (2 mg/kg diet for 10 days, providing an average of 0.04 mg clenbuterol/kg/d) increased body weight (7%), muscle mass (15% to 21%), and muscle protein content (9% to 26%), whereas epididymal fat pad weight and muscle glycogen content were reduced. During the withdrawal period, the greater body weight of ex-clenbuterol rats was sustained overall (ANOVA, P < .00005), but by day 10 this difference was no longer significant. At this point, gastrocnemius muscle mass was still higher (11%) when compared with that of control animals, but soleus muscle mass, muscle glycogen concentration, and epididymal fat pad weight had reverted to control values. These results were corroborated in a subsequent experiment using older rats. It was concluded that, unlike other beta-adrenoceptor-mediated effects, muscle protein accumulated during clenbuterol treatment can be maintained in certain muscles after removal of the drug for a period of time that is at least equivalent to the duration of treatment. This could have implications for the potential therapeutic use of this class of compound, and differences in the response observed between muscle types may help to elucidate the mechanisms responsible for the muscle protein deposition induced by clenbuterol. Copyright (C) 1994 by W.B. Saunders Company