Amelioration of capillary regression and atrophy of the soleus muscle in hindlimb‐unloaded rats by astaxanthin supplementation and intermittent loading

Abstract

New Findings r What is the central question of this study?We asked whether the combination of astaxanthin supplementation and intermittent loading would attenuate both the muscle atrophy and the capillary regression associated with chronic unloading. r What is the main finding and its importance?Intermittent loading alone attenuated atrophy of the soleus, while astaxanthin treatment alone maintained the capillary network in the soleus. The combination of these two interventions ameliorated both the muscle atrophy and the capillary regression induced by chronic unloading.A chronic decrease in neuromuscular activity (activation and/or loading) results in muscle atrophy and capillary regression that are due, in part, to the overproduction of reactive oxygen species. We have reported that antioxidant treatment with astaxanthin attenuates the overexpression of reactive oxygen species in atrophied muscles that, in turn, ameliorates capillary regression in hindlimb-unloaded rats. Astaxanthin supplementation, however, had little effect on muscle mass and fibre cross-sectional area. In contrast, intermittent loading of the hindlimbs of hindlimb-unloaded rats ameliorates muscle atrophy. Therefore, we hypothesized that the combination of astaxanthin supplementation and intermittent loading would attenuate both muscle atrophy and capillary regression during hindlimb unloading. As expected, 2 weeks of hindlimb unloading resulted in atrophy, a decrease in capillary volume and a shift towards smaller-diameter capillaries in the soleus muscle. Intermittent loading alone (1 h of cage ambulation per day) attenuated atrophy of the soleus, while astaxanthin treatment alone maintained the capillary network to near control levels. The combination of intermittent loading and astaxanthin treatment, however, ameliorated atrophy of the soleus and maintained the capillary volume and luminal diameters and the superoxide dismutase-1 protein levels near control values. These results indicate that intermittent loading combined with astaxanthin

Enterococcus faecium strain R30 increases red blood cell velocity and prevents capillary regression in the soleus of hindlimb‐unloaded rats via the eNOS/VEGF pathway

“…HU for 2 weeks resulted in capillary regression as reflected by reductions in capillary luminal diameter and volume (Figure ). These HU‐related changes in 3D capillary architecture are consistent with previous reports . Similarly, the observed decrease in C/F ratio in the soleus muscle of HU rats (Table ) is consistent with previous results .…”

“…The capillary regression appears to be an adaptation to a reduction in blood flow to the skeletal muscles caused by a decrease in oxidative demand with decreased neuromuscular activity . Intermitted periods of loading (exercise) attenuate the muscle atrophy associated with HU, but have little effect on the associated capillary regression . From a therapeutic point of view, these results indicate that the intermittent activity provided during the rehabilitation stage after a number of conditions involving muscle dysfunction may not suffice for restoring normal blood flow to the affected muscles.…”

“…In contrast, a reduction in the capillary network leads to exercise intolerance . A chronic decrease in neuromuscular activity, that is, a decrease in activation and/or loading, leads to capillary regression in skeletal muscles, especially in muscles having a high percentage of slow, oxidative fibers such as the soleus muscle . The capillary regression appears to be an adaptation to a reduction in blood flow to the skeletal muscles caused by a decrease in oxidative demand with decreased neuromuscular activity .…”

Astaxanthin intake attenuates muscle atrophy caused by immobilization in rats

“…We and others also showed that astaxanthin supplementation reduced up‐regulation of CuZn‐SOD expression and/or accumulation of ROS in response to hindlimb unloading with or without attenuating soleus muscle atrophy (Kanazashi et al. , ; Yoshihara et al. ).…”

Capillary growth and regression in skeletal muscle

“…Since earlier studies have suggested that anti-oxidative nutrients can attenuate skeletal capillary regression induced by disuse (Fig. 4) 32, 36) , it is thought that anti-oxidants may function as adjuvants to protect muscle endothelial cells from disuse atrophy.…”