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

TY - JOUR

T1 - Losartan has no additive effect on the response to heavy resistance exercise in human elderly skeletal muscle

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

N1 - doi: 10.1152/japplphysiol.00106.2018

PY - 2018/11

Y1 - 2018/11

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.

KW - Hypertrophy

KW - Muscle biopsy

KW - Muscle strength

KW - Satellite cells

UR - http://www.scopus.com/inward/record.url?scp=85057424877&partnerID=8YFLogxK

U2 - 10.1152/japplphysiol.00106.2018

DO - 10.1152/japplphysiol.00106.2018

M3 - Journal article

C2 - 30091666

SN - 8750-7587

VL - 125

SP - 1536

EP - 1554

JO - Journal of Applied Physiology

JF - Journal of Applied Physiology

IS - 5

ER -