Prazosin improves insulin-induced anabolic signaling by protecting capillary regression in the soleus muscle of hindlimb-unloaded rats.

Purpose: Reduced capillary number in skeletal muscle due to disuse can hinder the delivery of insulin and amino acid delivery to muscle cells, diminishing insulin activity and muscle protein synthesis, ultimately contributing to anabolic resistance. However, it remains unknown whether mitigating capillary regression during inactivity improves anabolic resistance. This study aimed to investigate the effect of increasing capillary number through the administration of prazosin, which can increase blood flow and prevent capillary regression, on anabolic resistance in skeletal muscle induced by disuse.

Methods: Male Sprague Dawley rats were divided into control and hindlimb unloading (HU) groups, with half of each group receiving prazosin (50 mg/L) in their drinking water for 2 weeks. Histological analysis of the soleus muscles was conducted to measure the capillary-to-fiber (C/F) ratio, while western blotting was performed to measure the activation of the Akt/mTORC1 muscle protein synthesis pathway before and after insulin stimulation.

Results: The C/F ratios were significantly lower in the HU and HU + Prz groups than in the control group but were significantly higher in the HU + Prz group than in the HU group. Following insulin stimulation, the phosphorylation levels of Akt, p70S6K, and S6RP increased in all groups, with a significantly greater increase observed in the HU + Prz group compared to the HU group, indicating improved molecular signaling related to muscle protein synthesis.

Conclusion: Administration of prazosin during hindlimb unloading mitigated capillary regression and enhanced insulin-stimulated muscle protein synthesis response. These findings suggest that enhancing capillary number may reduce the anabolic resistance caused by muscle disuse.

Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-024-01454-y.