Angiotensin II type 1a receptor deficiency alleviates muscle atrophy after denervation

Abstract

Abstract The study aim was to determine if suppressed activation of angiotensin II type 1 receptor (AT1) prevents severe muscle atrophy after denervation. The sciatic nerves in right and left inferior limbs were cut in AT1a knockout homo (AT1a−/−) male mice and wild-type (AT1a+/+) male mice. Muscle weight and cross-sectional areas of type IIb muscle fibers in gastrocnemius muscle decreased at 7 and 21 days postdenervation in both AT1a−/− mice and AT1a+/+ mice, and the reduction was significantly attenuated in the denervated muscles of AT1a−/− mice compared to the AT1a+/+mice. Gene expressions in the protein degradation system [two E3 ubiquitin ligases (muscle RING-finger protein-1 and Atrogin-1)] that were upregulated at 7days postdenervation in all denervated mice were significantly lower in AT1a−/− mice than in AT1a+/+mice. Activations of nuclear factor κB and Forkhead box subgroup O1 were significantly suppressed in the AT1a−/− mice compared with those in the AT1a+/+ mice. In addition, apoptosis pathway evaluated by gene expressions of Bcl-2-associated X protein and TUNEL staining was significantly suppressed in the AT1a−/− mice compared with that in the AT1a+/+ mice. In conclusion, the AT1 receptor deficiency retarded muscle atrophy after denervation via suppression ofthe protein degradation system and apoptosis.