Captopril treatment induces hyperplasia but inhibits myonuclear accretion following severe myotrauma in murine skeletal muscle

Adam P.W. Johnston, Leeann M. Bellamy, Michael de Lisio, Gianni Parise

Research output: Contribution to journalArticlepeer-review

Abstract

The role of ANG II in skeletal muscle and satellite cell regulation is largely unknown. Cardiotoxin (CTX) was used to investigate whether muscle injury activates a local ANG II signaling system. Following injury, immunohistochelmistry (IHC) analysis revealed a robust increase in the intensity of angiotensinogen and angiotensin type 1 (AT1) receptor expression. As regeneration proceeded, however, AT1 and angiotensinogen were downregulated. Nuclear accretion and fiber formation were also assessed during muscle regeneration in mice treated with captopril (an angiotensin-converting enzyme inhibitor). When ANG II formation was blocked through the use of captopril, we observed a significantly reduced accretion of nuclei into myofibers (25%), while tibialis anterior total fiber number was significantly increased 37%. This phenotype appeared to be due to alterations in satellite cell differentiation kinetics; captopril treatment led to sustained mRNA expression of markers associated with quiescence and proliferation (Myf5, Pax7) and simultaneously delayed or inhibited the expression of myogenin. IHC staining supported these findings, revealing that captopril treatment resulted in a strong trend (P 0.06) for a decrease in the proportion of myogenin-positive myoblasts. Furthermore, these observations were associated with a delay in muscle fiber maturation; captopril treatment resulted in sustained expression of embryonic myosin heavy chain. Collectively, these findings demonstrate that localized skeletal muscle angiotensin signaling is important to muscle fiber formation, myonuclear accretion, and satellite cell function.

Original languageEnglish (US)
Pages (from-to)R363-R369
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume301
Issue number2
DOIs
StatePublished - Aug 2011

Keywords

  • Angiotensin II
  • Differentiation
  • Muscle growth
  • Myonuclear accretion
  • Renin-angiotensin system
  • Satellite cell

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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