Angiotensin 1‐7 reduces muscle atrophy and function loss following 16 week denervation

Muscle atrophy is defined as a decrease in muscle mass that eventually leads to partial or complete muscle wasting. Muscle atrophy occurs in a variety of conditions including chronic diseases, limb immobilization and following a complete loss of muscle activity after spinal cord injury and peripheral nerve injury. A consequence of muscle atrophy is large force decrease associated with muscle mass loss as well as contractile components. The objective of this study was to determine whether angiotensin 1‐7 reduces the atrophy process and force loss following muscle denervation. Mouse extensor digitorum longus (EDL) and soleus were denervated by removing 3–4 mm of the sciatic nerve at the thigh level. Denervated mice were divided into 4 groups: i) denervated; ii) denervated and treated with angiotensin 1‐7; iii) denervated and treated with diminazene aceturate (DIZE), a ACE2 activator, to locally increase Ang 1‐7 levels, and iv) denervated and treated with sucrose. A 5 th group of mice was used as control, i.e., normal innervated muscle. The results show that angiotensin 1‐7 significantly prevented muscle mass loss and fully prevented the loss of normalized force to cross sectional area that normally occurs over a 16 week denervation period. The maintenance of the normalized maximum force by angiotensin 1‐7/DIZE was in part due to a prevention of the loss of membrane excitability that occurs because denervated fibers are depolarized. This study is thus providing evidence that angiotensin1, 7 has therapeutic potential to prevent function loss following prolonged denervation. Support or Funding Information This project was supported by a grant from the National Science and Engineering Research Council of Canada (NSERC).