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)] upregulated at 7 days 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, and protein expression of monocyte chemoattractant protein-1 were significantly suppressed in the AT1a−/− mice compared with those in the AT1a+/+ mice. In addition, suppressed apoptosis, lower infiltration of M1 macrophages, and higher infiltration of M2 macrophages were significantly observed at 21 days postdenervation in the AT1a−/− mice compared with those in the AT1a+/+ mice. In conclusion, the AT1 receptor deficiency retarded muscle atrophy after denervation.

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.

Background: The number of new dialysis patients, particularly among the elderly population, has been globally increasing. In Japan, patients aged ≥65 years and ≥75 years comprised 72% and 45% of patients on dialysis in 2018, respectively. Few studies have reported seasonal variations in the initiation of dialysis. We investigated the seasonal prevalence of the emergent hemodialysis initiation in the elderly.Methods: We reviewed 479 elderly patients who initiated hemodialysis between January 2006 and December 2018. Early elderly patients were defined as patients aged between 65 and 74 years, and late elderly patients were defined as those aged ≥75 years. Emergent hemodialysis initiation was defined as initiation with a temporary vascular catheter without elective permanent vascular access or unplanned hemodialysis initiation due to patients requiring critical care regardless of elective permanent vascular access. The information collected included age, sex, and details of the initiation of hemodialysis. Results: The early elderly group consisted of 199 patients, and the late elderly group consisted of 279 patients. In the late elderly group, hemodialysis initiation was most frequent in winter, followed by spring, autumn, and summer (p = 0.018). Moreover, emergent hemodialysis initiation was most frequent in winter, followed by spring, autumn, and summer (p = 0.009). Emergent hemodialysis initiation due to fluid overload was most frequent in winter, followed by autumn, spring, and summer (p < 0.001). Among late elderly patients who initiated hemodialysis, 78% did not have permanent hemodialysis access at the time of the initiation of hemodialysis. Conclusion: In the late elderly group, hemodialysis initiation and emergent hemodialysis initiation were significantly more frequent in the winter than in the remaining seasons. In addition, emergent hemodialysis initiation due to fluid overload was most frequent in winter in the late elderly group.