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

Am J Physiol Cell Physiol. 2022 Dec 1;323(6):C1681-C1696. doi: 10.1152/ajpcell.00271.2021. Epub 2022 Oct 24.


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 1) the extent of the Ang 1-7's hypertrophic effect in terms of muscle mass and muscle fiber cross-sectional area (CSA), 2) how Ang 1-7 affects muscle contractile function in terms of twitch and tetanic force, force-frequency relationship, and 3) whether the effect involves MasR. Wild-type and MasR-deficient [Mas receptor knockout mouse model (MasR-/-)] mice were treated with Ang 1-7 (100 ng/kg body wt·min using an osmotic pump) for 4 or 16 wk. Ang 1-7 significantly increased skeletal muscle/body weight ratio of soleus, tibialis, and gastrocnemius, but not of extensor digitorum longus (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 protein kinase B (Akt) and 4EBP proteins while having no effect on S6 phosphorylation, 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.

Keywords: cross-sectional area; fiber type; hypertrophy; skeletal muscle; tetanic force.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin I* / metabolism
  • Angiotensin I* / pharmacology
  • Animals
  • Mice
  • Mice, Inbred mdx
  • Muscle, Skeletal / metabolism
  • Peptide Fragments* / metabolism
  • Peptide Fragments* / pharmacology


  • angiotensin I (1-7)
  • Angiotensin I
  • Peptide Fragments