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Angiotensin 1-7 increases fiber cross sectional area and force in juvenile mouse skeletal muscle

Authors

  • H. Albadrani
  • T. Ammar
  • R. Rajgara
  • M. Bader
  • N. Wiper-Bergeron
  • J.M. Renaud

Journal

  • American Journal of Physiology Cell Physiology

Citation

  • Am J Physiol-Cell Physiol 323 (6): C1681-C1696

Abstract

  • Recent studies reported that in skeletal muscle angiotensin 1-7 (Ang 1-7), via its receptor Mas (MasR), prevents the atrophy induced by angiotensin II and by cast immobilization; it also improves muscle integrity and function in the mdx mouse, a muscular dystrophy model. The objectives of this study were to document i) the extent of the Ang 1-7's hypertrophic effect in terms of muscle mass and muscle fiber cross sectional area (CSA), ii) how Ang 1-7 affects muscle contractile function in terms of twitch and tetanic force, force-frequency relationship, and iii) whether the effect involves MasR. Wild type and MasR deficient (MasR(-/-)) mice were treated with Ang 1-7 (100 ng/kg body weight·min using an osmotic pump) for 4 or 16 weeks. Ang 1-7 significantly increased skeletal muscle/body weight ratio of soleus, tibialis and gastrocnemius, but not of EDL. It significantly increased fiber cross sectional area in the order of type I>IIA>IIB. In EDL and soleus muscles, it significantly increased twitch and tetanic force while causing a shift in the force-frequency relationship toward lower stimulation frequencies. It had no effect on fiber type composition. None of the Ang 1-7 effects observed in wild type mice were observed in MasR(-/-) muscles. It caused a transient increase in phosphorylated Akt and 4EBP proteins while having no effect on the phosphorylation of S6, MuRF-1 and atrogin-1 and a decrease in PAX7 expression in satellite cells. This is the first study demonstrating the hypertrophic effects of Ang 1-7 in normal muscle acting via its MasR.


DOI

doi:10.1152/ajpcell.00271.2021