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 p rotein (8%) and water (7%) content, but reduced food intake (4%) and e pididymal 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. Cl enbuterol-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 f at pad weight and muscle glycogen content were reduced. During the wit hdrawal period, the greater body weight of ex-clenbuterol rats was sus tained overall (ANOVA, P < .00005), but by day 10 this difference was no longer significant. At this point, gastrocnemius muscle mass was st ill higher (11%) when compared with that of control animals, but soleu s muscle mass, muscle glycogen concentration, and epididymal fat pad w eight had reverted to control values. These results were corroborated in a subsequent experiment using older rats. It was concluded that, un like other beta-adrenoceptor-mediated effects, muscle protein accumula ted during clenbuterol treatment can be maintained in certain muscles after removal of the drug for a period of time that is at least equiva lent to the duration of treatment. This could have implications for th e potential therapeutic use of this class of compound, and differences in the response observed between muscle types may help to elucidate t he mechanisms responsible for the muscle protein deposition induced by clenbuterol. Copyright (C) 1994 by W.B. Saunders Company