Losartan has no additive effect on the response to heavy-resistance exercise in human elderly skeletal muscle.

Our purpose here was to investigate the potential of blocking the angiotensin II type I receptor (AT1R) on the hypertrophy response of elderly human skeletal muscle to 4 mo of heavy-resistance exercise training. Fifty-eight healthy elderly men (+65 yr) were randomized into three groups, consuming either AT1R blocker (losartan, 100 mg/day) or placebo for 4 mo. Two groups performed resistance training (RT) and were treated with either losartan or placebo, and one group did not train but was treated with losartan. Quadriceps muscle biopsies, MR scans, and strength tests were performed at baseline and after 8 and 16 wk. Biopsies were sectioned for immunohistochemistry to determine the number of satellite cells, capillaries, fiber type distribution, and fiber area. Gene expression levels of myostatin, connective tissue, and myogenic signaling pathways were determined by real-time RT-PCR. Four months of heavy-resistance training led in both training groups to expected improvements in quadriceps (∼3-4%) and vastus lateralis (∼5-6%), cross-sectional area, and type II fiber area (∼10-18%), as well as dynamic (∼13%) and isometric (∼19%) quadriceps peak force, but with absolutely no effect of losartan on these outcomes. Furthermore, no changes were seen in satellite cell number with training, and most gene targets failed to show any changes induced by training or losartan treatment. We conclude that there does not appear to be any effect of AT1R blocking in elderly men during 4 mo of resistance training. Therefore, we do not find any support for using AT1R blockers for promoting muscle adaptation to training in humans. NEW & NOTEWORTHY Animal studies have suggested that blocking angiotensin II type I receptor (AT1R) enhances muscle regeneration and prevents disuse atrophy, but studies in humans are limited. Focusing on hypertrophy, satellite cells, and gene expression, we found that AT1R blocking did not result in any greater responses with 4 mo of resistance training. These results do not support previous findings and question the value of blocking AT1R in the context of preserving aging human muscle.

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 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.