Promoting skeletal muscle growth is extremely relevant to medical conditions in which muscle wasting contributes to low quality of life and high health care costs due to institutionalization. The proposed research would explore the possibility that angiotensin II (AII) positively mediates loading-induced skeletal muscle hypertrophy. This phenomenon occurs in cardiac muscle, but would be a completely novel finding in skeletal muscle tissue. Using the synergist ablation model of skeletal muscle hypertrophy in rats, the present experiment would determine if: 1) AII peptide and its precursors are up-regulated in skeletal muscle in response to increased loading, 2) inhibition of AII production by inhibiting angiotensin converting enzyme (ACE) prevents loading-induced skeletal muscle hypertrophy, and 3) AII receptors are present in skeletal muscle. Promising pilot data indicate that ACE inhibition may attenuate hypertrophy by at least 46 percent in this model. It is also proposed to measure an AII-responsive intracellular signaling pathway involving focal adhesion kinase and serum response factor, both of which are also necessary for loading-induced skeletal muscle hypertrophy. Identification of novel hormonal mechanisms promoting skeletal muscle growth may lead to drugs, gene medicine, or other countermeasures against skeletal muscle wasting.
