Effect of Losartan on the Acute Response of Human Elderly Skeletal Muscle to Exercise

Med Sci Sports Exerc. 2018 Feb;50(2):225-235. doi: 10.1249/MSS.0000000000001438.

Abstract

Purpose: To investigate the effect of blocking the angiotensin II Type I receptor (AT1R) upon the response to acute heavy-resistance exercise in elderly human skeletal muscle. The hypothesis was that AT1R blocking would result in a superior myogenic response accompanied by down-regulation of transforming growth factor-beta and up-regulation of insulin-like growth factor-1 signaling.

Methods: Twenty-eight healthy elderly men (+64 yr) were randomized into two groups, consuming either AT1R blocker (losartan, 100 mg·d) or placebo for 18 d before exercise. Participants performed one bout of heavy-unilateral-resistance exercise. Six muscle biopsies were obtained from the vastus lateralis muscles of each subject: two before exercise and four after exercise (4.5 h and 1, 4, and 7 d). Blood pressure and blood samples were collected at the same time points. Biopsies were sectioned for immunohistochemistry to determine the number of satellite cells associated with Type I and Type II fibers. Gene expression levels of Notch, connective tissue, and myogenic signaling pathways were determined by real-time reverse transcription polymerase chain reaction.

Results: Changes over time were detected for circulating creatine kinase, the number of satellite cells per Type I fiber, and most of the gene targets, with no specific effect of losartan on these. However, when compared with placebo, losartan intake resulted in a greater suppression of myostatin messenger RNA.

Conclusions: In general, there does not seem to be any effect of AT1R blocking on satellite cell number or myogenic pathways in elderly men in the days after one bout of heavy-resistance exercise. However, the greater suppression of myostatin may prove to be beneficial over a long-term intervention designed to induce hypertrophy.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Angiotensin II Type 1 Receptor Blockers / pharmacology
  • Double-Blind Method
  • Exercise*
  • Humans
  • Losartan / pharmacology*
  • Male
  • Middle Aged
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / physiology
  • Myostatin / metabolism
  • RNA, Messenger / metabolism
  • Resistance Training
  • Satellite Cells, Skeletal Muscle

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • MSTN protein, human
  • Myostatin
  • RNA, Messenger
  • Losartan