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

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 downregulation of TGF-[beta] and upregulation of IGF-1 signalling. Methods: 28 healthy elderly men (+64 years) were randomized into two groups, consuming either AT1R blocker (Losartan, 100mg/day) or Placebo for 18 days prior to 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 hours and 1, 4 and 7 days). 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 fibres. Gene expression levels of Notch, connective tissue and myogenic signalling pathways were determined by real time RT-PCR. Results: Changes over time were detected for circulating creatine kinase, the number of satellite cells per type I fibre 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 mRNA. Conclusion: In general, there does not appear to be any effect of AT1R blocking upon 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. (C) 2017 American College of Sports Medicine

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