Comparison of the effects of salbutamol and clenbuterol on skeletal muscle mass and carcass composition in senescent rats

Abstract

Aging decreases skeletal muscle mass and strength, making elderly subjects particularly vulnerable to catabolic effects of age-related diseases. Clenbuterol, a muscle anabolic β₂-adrenergic agonist, has reduced or restored skeletal muscle losses in experimental catabolic states. However, the doses of clenbuterol used to prevent or reverse muscle wasting in most animal models have exceeded the estimated safe dose in man. Recently, another β₂-adrenergic agonist, salbutamol (albuterol), has been shown to increase muscle weight and protein content in young rats at a dose similar to that used clinically. In contrast to clenbuterol, salbutamol is currently approved for human use as a bronchodilator in the United States. This study has compared the muscle and protein anabolic effects of salbutamol at a clinically relevant dose with those of clenbuterol at a dose typically used in animal models of muscle wasting. Salbutamol and clenbuterol were administered by implanted osmotic minipumps to Fischer-344 rats aged 3 and 24 months at doses of 1.03 mg and 600 μg per kilogram per 24 hours for 3 weeks. The weights of five hindlimb muscles, as well as carcass protein and fat content, were determined. Salbutamol and clenbuterol increased combined 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 protein content 20% and 30% in young rats, with 12% and 21% increases in old rats. Both agents increased carcass skeletal muscle protein content as calculated from carcass creatine content at both ages. In contrast, these agents reduced carcass fat content 12% and 26% in young rats, with 39% and 33% reductions in old rats. At the doses tested, salbutamol caused similar increases in muscle weight and protein content but smaller increases in carcass protein content compared with clenbuterol. In addition, both agents appeared to stimulate recovery of muscle protein lost following the stress of pump implantation in senescent rats. This study suggests that salbutamol, as well as clenbuterol, may be useful in stimulating muscle growth in elderly subjects with muscle wasting. Because it is currently approved for human use, salbutamol may be more readily available for human trial.