Effects of intermittent weight-bearing and clenbuterol on disuse atrophy of rat hindlimb muscles

Abstract

The present study was undertaken to evaluate the effects of intermittent weight-bearing (IWB) combined with β2-agonist clenbuterol (Cb) medication for suppressing muscle atrophy during progressive disuse atrophy. Male Wistar rats (age: 8weeks, body weight: 232 ± 14 g) were divided into a control group (CON) and an experimental group. The experimental group was further subdivided into a Cb medication group under normal conditions and a hindlimb unweighting (HU) treatment group. The HU treatment group was composed of four groups: HU treatment-only, HU treatment + IWB, HU treatment + Cb medication and HU treatment + IWB + Cb medication. IWB was performed by temporarily removing the suspension device for one hour daily. On Day 14, bilateral soleus muscle (SOL) and extensor digitorum longus muscle (EDL) were extracted. Muscles from the right side were used for the measurement of contractile properties (physiological functional evaluations). Muscles from the left side were used for histochemical and biochemical analysis. During HU, IWB combined with Cb medication worked to preserve the wet weight and relative weight of SOL as compared to CON. Its contractile properties were affected by weight-bearing, while the cross-sectional area of type I fiber and protein concentration were affected by Cb. This combined therapy had marked effects on the morphology of EDL, particularly on the cross-sectional area of type II fiber. The protein concentration and contractile properties of EDL were unaffected by this combined therapy. The effect of a combination of IWB and Cb medication was specific to fiber-type and region. The data suggested that 1) IWB was effective on functional aspects such as contractile properties and useful for physical therapy, 2) Cb medication exerted the atrophy-suppressive effect in morphological parameters and manifested less effect on functional aspects. The results in this study indicated the possibility of elevating the efficacy of IWB by Cb medication in SOL.