Does ACE inhibition enhance endurance performance and muscle energy metabolism in rats?

Bahi, Lahoucine; Koulmann, Nathalie; Sanchez, Hervé; Momken, Iman; Veksler, Vladimir; Bigard, A. X.; Ventura‐Clapier, Renée

doi:10.1152/japplphysiol.00323.2003

Cited by 30 publications

(27 citation statements)

References 50 publications

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“…1). The first protocol determined the sensitivity of mitochondrial respiration to various substrates in the presence of 2 mmol/l ADP, by cumulative substrate addition as described previously (21). The second protocol was aimed at determining the dependency of respiration on external [ADP] and [creatine] (22), with glutamate plus malate as substrates.…”

Section: The Generation Of Ampk␣2mentioning

confidence: 99%

AMP-Activated Protein Kinase α2 Deficiency Affects Cardiac Cardiolipin Homeostasis and Mitochondrial Function

et al. 2007

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AMP-activated protein kinase (AMPK) plays an important role in controlling energy homeostasis and is envisioned as a promising target to treat metabolic disorders. In the heart, AMPK is involved in short-term regulation and in transcriptional control of proteins involved in energy metabolism. Here, we investigated whether deletion of AMPK␣2, the main cardiac catalytic isoform, alters mitochondrial function and biogenesis. Body weight, heart weight, and AMPK␣1 expression were similar in control littermate and AMPK␣2 ؊/؊ mice. Despite normal oxygen consumption in perfused hearts, maximal oxidative capacity, measured using saponin permeabilized cardiac fibers, was ϳ30% lower in AMPK␣2 ؊/؊ mice with octanoate, pyruvate, or glutamate plus malate but not with succinate as substrates, showing an impairment at complex I of the respiratory chain. This effect was associated with a 25% decrease in mitochondrial cardiolipin content, the main mitochondrial membrane phospholipid that is crucial for complex I activity, and with a 13% decrease in mitochondrial content of linoleic acid, the main fatty acid of cardiolipins. The decrease in cardiolipin content could be explained by mRNA downregulation of rate-limiting enzymes of both cardiolipin synthesis (CTP:PA cytidylyltransferase) and remodeling (acyl-CoA:lysocardiolipin acyltransferase 1). These data reveal a new role for AMPK␣2 subunit in the regulation of cardiac muscle oxidative capacity via cardiolipin homeostasis. Diabetes 56: 786 -794, 2007

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Section: The Generation Of Ampk␣2mentioning

confidence: 99%

AMP-Activated Protein Kinase α2 Deficiency Affects Cardiac Cardiolipin Homeostasis and Mitochondrial Function

et al. 2007

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“…Taken together, these findings suggest that low ACE activity could have positive effects on muscle efficiency during exercise. This hypothesis has been previously tested in sedentary rats and ACE inhibition failed to affect the endurance capacity of animals during running exercise and/or the maximal oxidative capacity of skeletal muscles (3).…”

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confidence: 99%

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

Habouzit

Richard²,

Sanchez³

et al. 2009

Journal of Applied Physiology

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Habouzit E, Richard H, Sanchez H, Koulmann N, Serrurier B, Monnet R, Ventura-Clapier R, Bigard X. Decreased muscle ACE activity enhances functional response to endurance training in rats, without change in muscle oxidative capacity or contractile phenotype. J Appl Physiol 107: 346 -353, 2009. First published April 30, 2009 doi:10.1152/japplphysiol.91443.2008In the present study, we tested the hypothesis that chronic ANG I-converting enzyme (ACE) inhibition could improve the training-induced improvement in endurance exercise performance and that this could be related to enhanced skeletal muscle metabolic efficiency. Female Wistar rats were assigned to four groups comprising animals either maintained sedentary or endurance trained (Sed and Tr, respectively), and treated or not for 10 wk with an ACE inhibitor, perindopril (2 mg⅐kg Ϫ1 ⅐day Ϫ1) (Per and Ct, respectively) (n ϭ 8 each). Trained rats underwent an 8-wk treadmill training protocol that consisted of 2 h/day running at 30 m/min on a 8% decline. Before the start of and 1 wk before the end of experimental conditioning, the running time to exhaustion of rats was measured on a treadmill. The training program led to an increase in endurance time, higher in Tr-Per than in Tr-Ct group (125% in Tr-Ct vs. 183% in Tr-Per groups, P Ͻ 0.05). Oxidative capacity, measured in saponinpermeabilized fibers of slow soleus and fast plantaris muscles, increased with training, but less in Tr-Per than in Tr-Ct rats. The training-induced increase in citrate synthase activity also was less in soleus from Tr-Per than Tr-Ct rats. The training-induced increase in the percentage of the type IIa isoform of myosin heavy chain (MHC) (45%, P Ͻ 0.05) and type IIx MHC (25%, P Ͻ 0.05) associated with decreased type IIb MHC (34%, P Ͻ 0.05) was minimized by perindopril administration. These findings demonstrate that the enhancement in physical performance observed in perindopril-treated animals cannot be explained by changes in mitochondrial respiration and/or MHC distribution within muscles involved in running exercise. mitochondria; myosin heavy chain; angiotensin I-converting enzyme inhibitor; perindopril; running performance ENDURANCE TRAINING leads to molecular and cellular adaptations that mainly occur in the cardiovascular system and skeletal muscles and that improve performance during prolonged exercise. Skeletal muscle adaptation to endurance training includes quantitative and qualitative changes in mitochondria, marked development of muscle capillary network, and transition in isoforms of myosin heavy chain. Such training-induced changes contribute to improve aerobic capacity and reliance on oxidative metabolism to provide energy (for review, see Refs. 9 and 14). Individual responses to exercise training result from environmental factors (training program, altitude, nutrition) and are also obviously influenced by genetic factors (5). Recent advances in the sequencing of the human genome have strengthened efforts made to understand genetic differences that may explain individual respo...

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“…It is unlikely that ACEi directly affected the expression of PGC-1␣ because ACEi did not improve maximal oxidative capacity of skeletal muscles, nor endurance time in normal rats (1). Similarly, a direct negative effect of angiotensin II on the transcriptional regulation of muscular metabolism could probably be ruled out.…”

Section: Discussionmentioning

confidence: 98%

“…The treatment was administered 7 days/wk for 1 or 4 mo, the dose of PE being similar to that previously used (16). We did not study sham-operated rats treated with PE because ACEi did not modify healthy skeletal muscle mitochondrial function (1).…”

Section: Animalsmentioning

confidence: 99%

ACE inhibition prevents myocardial infarction-induced skeletal muscle mitochondrial dysfunction

Zoll¹,

Monassier²,

Garnier³

et al. 2006

Journal of Applied Physiology

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. ACE inhibition prevents myocardial infarction-induced skeletal muscle mitochondrial dysfunction. J Appl Physiol 101: [385][386][387][388][389][390][391] 2006. First published April 13, 2006; doi:10.1152/japplphysiol.01486.2005.-Heart failure is associated with alterations in cardiac and skeletal muscle energy metabolism resulting in a generalized myopathy. We investigated the molecular and cellular effects of angiotensin-converting enzyme inhibition (ACEi) on skeletal muscle metabolism in infarcted animals. Myocardial infarction (MI) was obtained by left descending coronary artery ligation. Sham, MI, and MI-treated rats (perindopril, 2 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 given 7 days after MI) were studied 1 and 4 mo after surgery. Oxygen consumption of white gastrocnemius (Gas) muscle was studied in saponin-permeabilized fibers, using the main substrates of mitochondrial respiration. mRNA expression of nuclear factors (PGC-1␣, NRF-2␣, and mtTFA), involved in the transcription of mitochondrial proteins, and of MCIP1, a marker of calcineurin activation, were also determined. Echocardiographic left ventricular fractional shortening was reduced in both MI and perindopril group after 1 and 4 mo, whereas systemic blood pressure was reduced by 16% only in the MI group after 4 mo. The capacity of Gas to oxidize glutamate-malate, glycerol-triphosphate, or pyruvate (Ϫ30%, P Ͻ 0.01; Ϫ32%, P Ͻ 0.05; Ϫ33%, P Ͻ 0.01, respectively), was greatly decreased. Furthermore, PGC-1␣ (Ϫ54%), NRF-2␣ (Ϫ45%), and MCIP1 (Ϫ84%) gene expression were significantly downregulated. ACEi improved survival, left ventricular function, and blood pressure. Perindopril protected also totally the Gas mitochondrial function and preserved the mRNAs concentration of the mitochondrial transcriptional factors. Moreover, PGC-1␣ correlated with Gas oxidative capacity (r ϭ 0.48), mitochondrial cytochrome-c oxidase (r ϭ 0.65), citrate synthase (r ϭ 0.45) activities, and MCIP1 expression (r ϭ 0.44). Thus ACEi totally prevented MI-induced alterations of skeletal muscle mitochondrial function and protein expression, halting the development of this metabolic myopathy. rehabilitation; mitochondria; angiotensin-converting enzyme inhibition CHRONIC HEART FAILURE (CHF) is characterized by impaired cardiac function, muscular fatigue, and reduced exercise tolerance. Reduction of exercise capacities involves not only the cardiovascular system but also the skeletal muscles themselves. Indeed, clinical and animal studies described muscular atrophy associated with fiber-type phenotype shift toward a more fast-twitch glycolytic phenotype during heart failure (14,23,24,26). Furthermore, impairments of mitochondrial function were observed in the heart and fast and slow skeletal muscles (3, 4) and were attributed to the downregulation of transcriptional coactivators and transcription factors implicated in mitochondrial biogenesis (PGC-1␣, NRF-2␣, and Tfam; Ref. 11).The generalized character of this metabolic myopathy suggests that humoral systemic factors could be involved (27). The renin-an...

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Does ACE inhibition enhance endurance performance and muscle energy metabolism in rats?

Cited by 30 publications

References 50 publications

AMP-Activated Protein Kinase α2 Deficiency Affects Cardiac Cardiolipin Homeostasis and Mitochondrial Function

AMP-Activated Protein Kinase α2 Deficiency Affects Cardiac Cardiolipin Homeostasis and Mitochondrial Function

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

ACE inhibition prevents myocardial infarction-induced skeletal muscle mitochondrial dysfunction

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