Angiotensin II is Necessary for Skeletal Muscle Regeneration Following Cardiotoxin‐induced Injury

Angiotensin II (Ang II) is a pleiotropic peptide involved in vasoactivity as well as cellular growth and proliferation. We examined whether Ang II is also a mediator of muscle regeneration by administering an ACE inhibitor (captopril) following cardiotoxin (ctx)‐induced muscle injury in C57BL/6 mice. 10 days following ctx injection, captopril treated mice demonstrated a delayed response in the myogenic program evidenced by sustained expression of Pax7 and Myf5 transcripts while myogenin mRNA, a marker of differentiating myoblasts, was significantly inhibited. This delay was also evident at the myofibre level with captopril treated mice exhibiting a significant ~3.5 fold elevation in eMHC gene expression. Importantly, newly formed fibres in the captopril treated group demonstrated an impaired hypertrophic response as fibre cross‐sectional area (CSA) from day 10 to day 21 was increased by 81% in the control group and only 27% in the captopril group. This resulted in an overall difference of 25% in CSA between groups at day 21 post injury. These effects do not appear to be due to a deficiency in protein synthesis as myonuclear domain size was unchanged between groups. Rather, there appears to be a loss of satellite cell content as the captopril treated group demonstrated a ~29% decrease in Pax7+ cells by day 21 post injury. This research was supported by NSERC.