T.P.11 Effect of formoterol, a selective β2 adrenoceptor agonist, against nerve injury-induced muscle disuse atrophy

Abstract

Skeletal muscle atrophy is common, debilitating and without acceptable treatment options. In humans, skeletal muscle atrophy occurs under various physiological and disease conditions, such as injury resulting in immobilization, critical illness, burns, cancer, COPD, liver disease, AIDS, congestive heart failure, diabetes. The reduction in strength and endurance associated with the involuntary loss of muscle mass results in functional limitations, loss of independence, reduced quality of life, increased disability, and increased mortality. Selective β2 adrenoceptor agonists, such as formoterol, elicit skeletal muscle hypertrophy, which is associated with increased force producing capacity in both fast- and slow-twitch muscles. Hypertrophy can be blocked by selective β2 adrenoceptor antagonist or genetic deletion of the β2 adrenoceptor. Several studies have shown potential efficacy of β2 adrenoceptor agonists in addressing muscle wasting in many animal species and humans. In this report, the effect of formoterol against a rodent model of muscle disuse atrophy was evaluated. The disuse atrophy was induced by cuff crushing-based nerve injury which is leading to neuropathic pain and eventually muscle disuse. It is known that selective β2 adrenoceptor agonists are effective against neuropathic pain, although the effect on muscle atrophy and function has not been evaluated yet. Therefore, formoterol was tested in this model in both prevention and therapeutic modes. The disuse atrophy was significantly prevented, and recovery from the atrophy was also significantly promoted by the formoterol treatment. In conclusion, formoterol is effective in the nerve injury-induced muscle disuse atrophy, and selective β2 adrenoceptor agonists might be a potential therapeutic option for treating muscle atrophy conditions caused by disuse and immobilization due to injury and critical illness.