Decreased muscle ACE activity enhances functional response to endurance training in rats, without change in muscle oxidative capacity or contractile phenotype

Habouzit, Estelle; Richard, Hélène; Sanchez, Hervé; Koulmann, Nathalie; Serrurier, B.; Monnet, Rachel; Ventura‐Clapier, Renée; Bigard, Xavier

doi:10.1152/japplphysiol.91443.2008

Cited by 23 publications

(19 citation statements)

References 34 publications

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“…The effect of these medications on the adaptation to training is unclear. Whereas some studies suggest that ACE activity may modify the adaptive response to training (69), more recent studies suggest that this is not related to modification of mitochondrial biology (19). Moreover, we should note that whether these medications affect mitochondrial structure/function is controversial (38,70), and there are no data regarding their effects on the mitochondrial adaptations to resistance training.…”

Section: Discussionmentioning

confidence: 93%

Skeletal muscle mitochondrial density, gene expression, and enzyme activities in human heart failure: minimal effects of the disease and resistance training

Toth

Miller

Ward

et al. 2012

Journal of Applied Physiology

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Toth MJ, Miller MS, Ward KA, Ades PA. Skeletal muscle mitochondrial density, gene expression, and enzyme activities in human heart failure: minimal effects of the disease and resistance training. J Appl Physiol 112: 1864 -1874, 2012. First published March 29, 2012 doi:10.1152/japplphysiol.01591.2011.-Impaired skeletal muscle energetics could adversely affect physical and metabolic function in patients with heart failure (HF). The effect of HF on aspects of mitochondrial structure and function, independent of muscle disuse and other disease-related confounding factors, however, is unclear. Moreover, no study has evaluated whether resistance exercise training, a modality that increases functional capacity, might derive its benefits through modulation of mitochondrial structure and function. Thirteen HF patients and 14 age-and physical activity-matched controls were evaluated for skeletal muscle mitochondrial size/content, gene expression, and enzyme activity before and after an 18-wk resistance exercise-training program. At baseline, HF patients and controls had similar mitochondrial fractional areas, although HF patients had larger average mitochondrion size (P Ͻ 0.05) and a trend toward a reduced number of mitochondria (P Յ 0.10). No differences in the expression of transcriptional regulators or cytochrome oxidase subunits or the activity of mitochondrial and cytosolic enzymes were noted. Relationships among transcriptional regulators suggested that networks controlling mitochondrial content and gene expression are intact. Resistance training increased (P Ͻ 0.01) mitochondrial transcription factor A expression in patients and controls, and this increase was related to improvements in muscle strength (P ϭ 0.05). Training did not, however, alter mitochondrial size/content, enzyme activities, or expression of other transcriptional regulators. In conclusion, our results suggest that the HF syndrome has minimal effects on skeletal muscle mitochondrial biology when the confounding effects of muscle disuse and other disease-related factors are removed. Moreover, the beneficial effects of resistance training on physical function in HF patients and controls are likely not related to alterations in mitochondrial biology. oxidative metabolism; ultrastructure; physical disability IMPAIRED SKELETAL MUSCLE ENERGETICS in heart failure (HF) patients (32) may contribute to physical disability and metabolic dysfunction. Decreased skeletal muscle oxidative capacity (63), secondary to reduced mitochondrial density (12, 13) and/or function (10, 36, 52), may contribute to exercise intolerance, the hallmark symptom of HF. Moreover, as mitochondrial dysfunction is associated with fiber atrophy (7), impaired energetics may reduce physical function by promoting muscle wasting and, in turn, weakness (21). Because mitochondrial dysfunction has been implicated in the pathophysiology of diabetes (41), alterations in mitochondrial content and/or function could also contribute to the high prevalence of insulin resistance in the HF population ...

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Section: Discussionmentioning

confidence: 93%

Skeletal muscle mitochondrial density, gene expression, and enzyme activities in human heart failure: minimal effects of the disease and resistance training

Toth

Miller

Ward

et al. 2012

Journal of Applied Physiology

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“…However, in a small study of 36 older men with hypertension, endurance increased in those receiving ACEi (28), and our previous randomized controlled trial in functionally impaired people showed that 20 weeks of ACEi treatment significantly improved 6MWD by 31.6 m compared with placebo and resulted in a clinically significant improvement in quality of life (6). In rodents, improvements in performance with ACEi in combination with exercise but not with ACEi alone have been reported (29), but the evidence is not consistent (30,31). …”

Section: Discussionmentioning

confidence: 99%

Do ACE Inhibitors Improve the Response to Exercise Training in Functionally Impaired Older Adults? A Randomized Controlled Trial

Sumukadas

Band

Miller³

et al. 2013

The Journals of Gerontology Series A: Biological Sciences and M

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Background.Loss of muscle mass and strength with ageing is a major cause for falls, disability, and morbidity in older people. Previous studies have found that angiotensin-converting enzyme inhibitors (ACEi) may improve physical function in older people. It is unclear whether ACEi provide additional benefit when added to a standard exercise training program. We examined the effects of ACEi therapy on physical function in older people undergoing exercise training.Methods.Community-dwelling people aged ≥65 years with functional impairment were recruited through general (family) practices. All participants received progressive exercise training. Participants were randomized to receive either 4 mg perindopril or matching placebo daily for 20 weeks. The primary outcome was between-group change in 6-minute walk distance from baseline to 20 weeks. Secondary outcomes included changes in Short Physical Performance Battery, handgrip and quadriceps strength, self-reported quality of life using the EQ-5D, and functional impairment measured using the Functional Limitations Profile.Results.A total of 170 participants (n = 86 perindopril, n = 84 placebo) were randomized. Mean age was 75.7 (standard deviation [SD] 6.8) years. Baseline 6-minute walk distance was 306 m (SD 99). Both groups increased their walk distance (by 29.6 m perindopril, 36.4 m placebo group) at 20 weeks, but there was no statistically significant treatment effect between groups (−8.6m [95% confidence interval: −30.1, 12.9], p = .43). No statistically significant treatment effects were observed between groups for the secondary outcomes. Adverse events leading to withdrawal were few (n = 0 perindopril, n = 4 placebo).Interpretation.ACE inhibitors did not enhance the effect of exercise training on physical function in functionally impaired older people.

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“…13 Similarly, it was recently reported that the addition of ACEis potentiated exercise-mediated improvements in physical performance in older rats. 14,15 Both of these studies reported that the addition of ACEis potentiated the beneficial effects of aerobic training on exercise tolerance determined according to treadmill endurance. These preclinical findings add to an extensive literature from genetic studies of humans indicating an important interaction between the renin–angiotensin system and physical performance.…”

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confidence: 99%

Angiotensin‐Converting Enzyme Inhibitor Use by Older Adults Is Associated with Greater Functional Responses to Exercise

Buford

Manini

Hsu

et al. 2012

J American Geriatrics Society

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OBJECTIVES To assess the association between angiotensin converting enzyme inhibitors (ACEis) and improvements in the physical function of older adults in response to chronic exercise training. DESIGN Secondary analysis of the Lifestyle Interventions and Independence for Elders Pilot (LIFE-P) study, a multisite randomized clinical trial to evaluate the effects of chronic exercise on the physical function of older adults at risk for mobility disability. SETTING Four academic research centers within the United States. PARTICIPANTS Four hundred twenty-four individuals aged 70 to 89 with mild to moderate functional impairments categorized for this analysis as ACEi users, users of other antihypertensive drugs, or antihypertensive nonusers. INTERVENTION A 12-month intervention of structured physical activity (PA) or health education promoting successful aging (SA). MEASUREMENTS Change in walking speed during a 400-m test and performance on a battery of short-duration mobility tasks (Short Physical Performance Battery (SPPB)). RESULTS Physical activity significantly improved the adjusted walking speed of ACEi users (P < .001) but did not of nonusers. PA improved the adjusted SPPB score of ACEi users (P < .001) and of persons who used other antihypertensive drugs (P = .005) but not of antihypertensive nonusers (P = .91). The percentage of ACEi users deriving clinically significant benefit from exercise training for walking speed (30%) and SPPB score (48%) was dramatically higher than for nonusers (14% and 12%, respectively). CONCLUSION For older adults at risk for disability, exercise-derived improvements in physical function were greater for ACEi users than users of other antihypertensive drugs and antihypertensive nonusers.

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Decreased muscle ACE activity enhances functional response to endurance training in rats, without change in muscle oxidative capacity or contractile phenotype

Cited by 23 publications

References 34 publications

Skeletal muscle mitochondrial density, gene expression, and enzyme activities in human heart failure: minimal effects of the disease and resistance training

Skeletal muscle mitochondrial density, gene expression, and enzyme activities in human heart failure: minimal effects of the disease and resistance training

Do ACE Inhibitors Improve the Response to Exercise Training in Functionally Impaired Older Adults? A Randomized Controlled Trial

Angiotensin‐Converting Enzyme Inhibitor Use by Older Adults Is Associated with Greater Functional Responses to Exercise

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