Improvement of exercise capacity of rats with chronic heart failure by long‐term treatment with trandolapril

Yamaguchi, Fuminari; Kawana, Ken-ichiro; Tanonaka, Kouichi; Kamano, Isamu; Igarashi, Takahiro; Gen, Eigyoku; Fujimoto, Yoko; Maki, Toshihide; Sanbe, Atsushi; Nasa, Yoshihisa; Takeo, Satoshi

doi:10.1038/sj.bjp.0702471

Cited by 16 publications

(14 citation statements)

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“…Whether the pharmacological inhibition of ACE affects the mitochondrial function has been previously studied. Prolonged ACE inhibition completely prevented the decreased skeletal muscle oxidative capacity expected in patients with chronic heart failure (10) and in rats with heart failure secondary to myocardial infarction (32,35). However, this protective effect of ACE inhibition remains controversial, and perindopril administration failed to restore muscle oxidative capacity and mitochondrial function in a rat model of heart failure induced by aortic stenosis (16) or in a rat model of type I diabetes (22).…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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

View full text Add to dashboard Cite

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“…Left anterior descending coronary artery ligation was used to produce myocardial infarction and consequent HF in rats, as this model has been shown to have significant reductions in exercise capacity (Yamaguchi et al, 1999;Pfeifer et al, 2001;Koh et al, 2003). Alterations in skeletal muscle Ca 21 sensitivity and handling have also been noted with heart failure (Ward et al, 2003;Kho et al, 2012b), and pharmacological calcium sensitizers have previously been shown to increase calcium sensitivity in diaphragms from heart failure rats (van Hees et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

The Small-Molecule Fast Skeletal Troponin Activator, CK-2127107, Improves Exercise Tolerance in a Rat Model of Heart Failure

Hwee

Kennedy

Hartman

et al. 2015

The Journal of Pharmacology and Experimental Therapeutics

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Heart failure-mediated skeletal myopathy, which is characterized by muscle atrophy and muscle metabolism dysfunction, often manifests as dyspnea and limb muscle fatigue. We have previously demonstrated that increasing Ca 21 sensitivity of the sarcomere by a small-molecule fast skeletal troponin activator improves skeletal muscle force and exercise performance in healthy rats and models of neuromuscular disease. The objective of this study was to investigate the effect of a novel fast skeletal troponin activator, CK-2127107 (2-aminoalkyl-5-N-heteroarylpyrimidine), on skeletal muscle function and exercise performance in rats exhibiting heart failure-mediated skeletal myopathy. Rats underwent a left anterior descending coronary artery ligation, resulting in myocardial infarction and a progressive decline in cardiac function [left anterior descending coronary artery heart failure (LAD-HF)]. Compared with sham-operated control rats, LAD-HF rat hindlimb and diaphragm muscles exhibited significant muscle atrophy. Fatigability was increased during repeated in situ isokinetic plantar flexor muscle contractions. CK-2127107 produced a leftward shift in the force-Ca 21 relationship of skinned, single diaphragm, and extensor digitorum longus fibers. Exercise performance, which was assessed by rotarod running, was lower in vehicle-treated LAD-HF rats than in sham controls (116 6 22 versus 193 6 31 seconds, respectively; mean 6 S.E.M.; P 5 0.04). In the LAD-HF rats, a single oral dose of CK-2127107 (10 mg/kg p.o.) increased running time compared with vehicle treatment (283 6 47 versus 116 6 22 seconds; P 5 0.0004). In summary, CK-2127107 substantially increases exercise performance in this heart failure model, suggesting that modulation of skeletal muscle function by a fast skeletal troponin activator may be a useful therapeutic in heart failure-associated exercise intolerance.

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“…The animals were submitted to physical exercise on the treadmill (Yamaguchi et al, 1999), with the exception of an extra group, which did not exercise (control without stress). The fatigue protocol consisted of a 3 min run to warm-up at 4 m/min, 3 min at 8 m/min, 9 min at 14 m/min, 5 min at 20 m/min, 5 min at 26 m/min and finally 5 min at 32 m/min.…”

Section: Animalsmentioning

confidence: 99%

Evaluation of Baccharis trimera and Davilla rugosa in tests for adaptogen activity

Mendes

Tabach

Carlini

2007

Phytotherapy Research

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Baccharis trimera (Asteraceae) and Davilla rugosa (Dilleniaceae) are used popularly as tonics, aphrodisiacs and for stomach ailments, among other uses. Hydroalcohol extracts of the aerial parts of both plants were investigated with regard to their chemical constitution and their pharmacological activity in tests that evaluate adaptogen activity. Alkaloids, flavonoids, saponins, polyphenols/tannins and coumarins were identified in both extracts, while lignans were found only in the extract of Davilla rugosa. This extract presented also a marked antioxidant activity and exerted a moderate antiulcer effect in rats submitted to cold immobilization stress. It did not, however, inhibit the increase in the levels of ACTH and corticosterone induced by stress. Moreover, the Davilla rugosa did not improve the physical performance of mice submitted to forced exercise and the learning time of old rats in the T-maze, neither did it reduce the blood viscosity of the old animals. Conversely, the Baccharis trimera extract only presented a moderate antioxidant activity, without any positive effect on the other tests. These results point to the absence of an adaptogen activity of Baccharis trimera, with some effects that could be related to such an activity as regards the Davilla rugosa.

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Improvement of exercise capacity of rats with chronic heart failure by long‐term treatment with trandolapril

Cited by 16 publications

References 31 publications

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

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

The Small-Molecule Fast Skeletal Troponin Activator, CK-2127107, Improves Exercise Tolerance in a Rat Model of Heart Failure

Evaluation of Baccharis trimera and Davilla rugosa in tests for adaptogen activity

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