Exposure to reduced activity induces skeletal muscle atrophy. Oxidative stress might contribute to muscle wasting via proteolysis activation. This study aimed to test two hypotheses in rats. First, supplementation of the antioxidant vitamin E, prior and during the phase of unloading, would partly counteract unloading-induced soleus muscle atrophy. Secondly, vitamin E supplementation would decrease the rate of muscle proteolysis by reducing expression of calpains, caspases-3, -9, and -12, and E3 ubiquitin ligases (MuRF1 and MAFbx). Soleus muscle atrophy (-49%) induced by 14 days of hindlimb unloading was reduced to only 32% under vitamin E. Vitamin E partly prevented the decrease in type I and IIa fiber size. Supplementation increased HSP72 content and suppressed the rise in muscle level of thiobarbituric acid-reactive substance caused by unloading but failed to modify the lower ratio of reduced vs oxidized glutathione, the higher uncoupling proteins mRNA, and the antioxidant enzyme activities (superoxide dismutase, catalase, and glutathione peroxidase) observed after unloading. Vitamin E treatment abolished the large upregulation of caspases-9 and -12 and MuRF1 transcripts in unloaded muscle and greatly decreased the upregulation of mu-calpain, caspase-3, and MAFbx mRNA. In conclusion, the protective effect of vitamin E might be due to modulation of muscle proteolysis-related genes rather than to its antioxidant function.

The effects of bed rest on the cardiovascular and muscular parameters which affect maximal O2 consumption (VO2,max) were studied. The fractional limitation of VO2,max imposed by these parameters after bed rest was analysed. The VO2,max, by standard procedure, and the maximal cardiac output (Q̇max), by the pulse contour method, were measured during graded cyclo‐ergometric exercise on seven subjects before and after a 42‐day head‐down tilt bed rest. Blood haemoglobin concentration ([Hb]) and arterialized blood gas analysis were determined at the highest work load. Muscle fibre types, oxidative enzyme activities, and capillary and mitochondrial densities were measured on biopsy samples from the vastus lateralis muscle before and at the end of bed rest. The measure of muscle cross‐sectional area (CSA) by NMR imaging at the level of biopsy site allowed computation of muscle oxidative capacity and capillary length. The VO2max was reduced after bed rest (−16.6%). The concomitant decreases in Q̇max (−30.8%), essentially due to a change in stroke volume, and in [Hb] led to a huge decrease in O2 delivery (−39.7%). Fibre type distribution was unaffected by bed rest. The decrease in fibre area corresponded to the significant reduction in muscle CSA (−17%). The volume density of mitochondria was reduced after bed rest (−16.6%), as were the oxidative enzyme activities (−11%). The total mitochondrial volume was reduced by 28.5%. Capillary density was unchanged. Total capillary length was 22.2% lower after bed rest, due to muscle atrophy. The interaction between these muscular and cardiovascular changes led to a smaller reduction in VO2max than in cardiovascular O2 transport. Yet the latter appears to play the greatest role in limiting VO2max after bed rest (>70% of overall limitation), the remaining fraction being shared between peripheral O2 diffusion and utilization.

The purpose of this study was to investigate alterations in structural and functional properties in the soleus (SOL) and extensor digitorum longus (EDL) muscles of rats after 1, 2, and 5 wk of tail suspension. Maximal O2 uptake was 19% lower after 5 wk suspension. Loss of muscle mass was greater in SOL (63%) than in EDL (22%) muscle. A reduction of type I distribution was accompanied by an increase of intermediate fiber subgroups (int I in SOL, int II in EDL). The cross-sectional area of all three fiber types was reduced by hypokinesia. The decrease in capillaries per fiber in SOL was greater than the decrease in citrate synthase and 3-hydroxyacyl-CoA dehydrogenase activities after 5 wk. No alteration in lactate dehydrogenase activity was noted. In EDL, no changes in fiber area, capillarization, and enzymatic activities occurred. Energy charge remained unchanged (0.91) whatever the muscle. These results suggest that type I fibers showed an earlier and greater susceptibility than type II fibers to suspension which is also accompanied by a decreased aerobic capacity.