COMPARISON OF THE EFFECTS OF SALBUTAMOL AND CLENBUTEROL ON SKELETAL-MUSCLE MASS AND CARCASS COMPOSITION IN SENESCENT RATS

Aging decreases skeletal muscle mass and strength, making elderly subj ects particularly vulnerable to catabolic effects of age-related disea ses. Clenbuterol, a muscle anabolic beta(2)-adrenergic agonist, has re duced or restored skeletal muscle losses in experimental catabolic sta tes. However, the doses of clenbuterol used to prevent or reverse musc le wasting in most animal models have exceeded the estimated safe dose in man. Recently, another beta(2)-adrenergic agonist, salbutamol (alb uterol), has been shown to increase muscle weight and protein content in young rats at a dose similar to that used clinically. In contrast t o clenbuterol, salbutamol is currently approved for human use as a bro nchodilator in the United States. This study has compared the muscle a nd protein anabolic effects of salbutamol at a clinically relevant dos e with those of clenbuterol at a dose typically used in animal models of muscle wasting. Salbutamol and clenbuterol were administered by imp lanted osmotic minipumps to Fischer-344 rats aged 3 and 24 months at d oses of 1.03 mg and 600 mu g per kilogram per 24 hours for 3 weeks. Th e weights of five hindlimb muscles, as well as carcass protein and fat content, were determined. Salbutamol and clenbuterol increased combin ed hindlimb muscle weight 19% and 28% in young rats, with 19% and 25% increases in old rats. Similarly, these drugs increased gastrocnemius weight and protein content 19% and 24% in young rats, with 19% and 23% increases in old rats. Salbutamol and clenbuterol increased carcass p rotein content 20% and 30% in young rats, with 12% and 21% increases i n old rats. Both agents increased carcass skeletal muscle protein cont ent as calculated from carcass creatine content at both ages. In contr ast, these agents reduced carcass fat content 12% and 26% in young rat s, with 39% and 33% reductions in old rats. At the doses tested, salbu tamol caused similar increases in muscle weight and protein content bu t smaller increases in carcass protein content compared with clenbuter ol. In addition, both agents appeared to stimulate recovery of muscle protein lost following the stress of pump implantation in senescent ra ts. This study suggests that salbutamol, as well as clenbuterol, may b e useful in stimulating muscle growth in elderly subjects with muscle wasting. Because it is currently approved for human use, salbutamol ma y be more readily available for human trial. Copyright (C) 1994 by W.B . Saunders Company