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

Mette F Heisterberg; Jesper Løvind Andersen; Peter Schjerling; Alberte Lund; Simone Dalskov; Anders Overgård Jønsson; Nichlas Warming; Mathilde Fogelstrøm; Michael Kjaer; Abigail Louise Mackey

doi:10.1152/japplphysiol.00106.2018

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

Mette F Heisterberg, Jesper Løvind Andersen, Peter Schjerling, Alberte Lund, Simone Dalskov, Anders Overgård Jønsson, Nichlas Warming, Mathilde Fogelstrøm, Michael Kjaer, Abigail Louise Mackey

8 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Journal of Applied Physiology
Volume	125
Issue number	5
Pages (from-to)	1536-1554
Number of pages	19
ISSN	8750-7587
DOIs	https://doi.org/10.1152/japplphysiol.00106.2018
Publication status	Published - Nov 2018

Keywords

Hypertrophy
Muscle biopsy
Muscle strength
Satellite cells

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10.1152/japplphysiol.00106.2018

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Heisterberg, M. F., Andersen, J. L., Schjerling, P., Lund, A., Dalskov, S., Overgård Jønsson, A., Warming, N., Fogelstrøm, M., Kjaer, M., & Mackey, A. L. (2018). Losartan has no additive effect on the response to heavy resistance exercise in human elderly skeletal muscle. Journal of Applied Physiology, 125(5), 1536-1554. https://doi.org/10.1152/japplphysiol.00106.2018

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title = "Losartan has no additive effect on the response to heavy resistance exercise in human elderly skeletal muscle",

abstract = "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.",

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AU - Heisterberg, Mette F

AU - Andersen, Jesper Løvind

AU - Schjerling, Peter

AU - Lund, Alberte

AU - Dalskov, Simone

AU - Overgård Jønsson, Anders

AU - Warming, Nichlas

AU - Fogelstrøm, Mathilde

AU - Kjaer, Michael

AU - Mackey, Abigail Louise

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PY - 2018/11

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N2 - 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.

AB - 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.

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

Abstract

Keywords

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