Oxidative stress is related to exercise intolerance in patients with heart failure

Nishiyama, Yasuhiro; Ikeda, Hisao; Haramaki, Nobuya; Yoshida, Noriko; Imaizumi, Tsutomu

doi:10.1016/s0002-8703(98)70351-5

Cited by 122 publications

(69 citation statements)

References 25 publications

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“…These data raise the interesting possibility that increased ROSafter myocardial infarction can be a stimulus for myocardial MMP activation, which might play an important role in the development of HE Oxidative Stress and Skeletal Muscle Dysfunction Oxidative stress could be the mechanistic basis for muscle fatigue and reduced exercise tolerance in HF patients (27). This notion is supported by a positive correlation between ROSand exercise intolerance in these patients (28). The production of ROSwas increased in the skeletal muscle homogenates obtained from a murine model of HFand increased ROSwere identified as -OH originating from O2~, which was associated with a concomitant increase in the oxidation of lipids (29).…”

Section: Oxidative Stress and Myocardial Damagementioning

confidence: 83%

Oxidative Stress in Heart Failure: The Role of Mitochondria.

Tsutsui

2001

Intern. Med.

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Recent experimental and clinical studies have suggested that oxidative stress is enhanced in heart failure. The production of oxygen radicals is increased in the failing heart whereas antioxidant enzymeactivities are preserved. Mitochondrial electron transport is an enzymatic source of oxygenradical generation and also a target against oxidantinduced damage. Chronic increases in oxygen radical production in the mitochondriacan lead to a catastrophic cycle of mitochondrial DNAdamage as well as functional decline, further radical generation, and cellular injury. These cellular events might play an important role in the development and progression of myocardial remodeling and failure.

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Section: Oxidative Stress and Myocardial Damagementioning

confidence: 83%

Oxidative Stress in Heart Failure: The Role of Mitochondria.

Tsutsui

2001

Intern. Med.

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“…30,31 Oxidative stress has been shown to be related to exercise intolerance in patients with HF. 13 Furthermore, Tsutsui et al 14 have reported that reactive oxygen species are increased in skeletal muscle in HF after myocardial infarction and that they originate from O 2 Ϫ produced by mitochondrial oxidase. Thus, oxygen free radicals play an important role in the limitation of exercise capacity.…”

Section: Discussionmentioning

confidence: 99%

“…12 Recently, increased oxidative stress has been shown to be related to the limitation of exercise capacity in patients with HF. 13 Tsutsui et al 14 have reported that reactive oxygen species are increased in skeletal muscle in HF after myocardial infarction and that they originate from superoxide anion (O 2 Ϫ ) produced by mitochon-drial oxidase. O 2 Ϫ reacts rapidly with NO, reducing NO bioactivity and producing the oxidant peroxynitrite.…”

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confidence: 99%

Limited Exercise Capacity in Heterozygous Manganese Superoxide Dismutase Gene–Knockout Mice

et al. 2005

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Background-We have reported that there is a limitation of exercise capacity in mice with defects in the expression of endothelial nitric oxide (NO) synthase, which is associated with a greater increase in whole-body oxygen consumption (V O 2 ). We hypothesized that in states in which superoxide anion (O 2 Ϫ ) is increased, especially in the mitochondria, whole-body V O 2 will be increased because of the inactivation of NO, and consequently, exercise capacity will be reduced. Methods and Results-Heterozygous manganese superoxide anion dismutase (SOD2) gene-knockout mice (SOD2 ϩ/Ϫ ), in which SOD2 activity is reduced by 30% to 80%, and wild-type control mice (SOD2 ϩ/ϩ ) were treadmill-tested to measure indices defining exercise capacity. Tempol was given to each mouse for 7 days by an intraperitoneal injection to scavenge O 2 Ϫ before a second treadmill testing. V O 2 and carbon dioxide production (V CO 2 ) at rest were increased in SOD2 ϩ/Ϫ . The work (vertical distance run ϫ body weight) to exhaustion was decreased in SOD2 ϩ/Ϫ . When the maximum V O 2 and V CO 2 were corrected to per work unit, they were increased in SOD2 ϩ/Ϫ . Tempol normalized basal V O 2 and V CO 2 and improved the work to exhaustion and corrected V O 2 and V CO 2 in SOD2 ϩ/Ϫ . V O 2 of skeletal muscle was measured in vitro. Bradykinin-induced reduction in V O 2 in vitro was attenuated in SOD2 ϩ/Ϫ , and was acutely restored by Tempol. There was a decrease in SOD2 protein level and a concomitant increase in lucigenin-detectable O 2

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“…Protection against oxidative stress is often linked with improved exercise tolerance (Nishiyama et al ., 1998; Fisher‐Wellman et al ., 2009; Ryan et al ., 2010). Paraquat, which increases oxidative stress, reduced WT exercise capacity by 40%, and significantly less, P < 0.05 , that is, by only 7% in AC5 KO (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…As enhanced exercise can result from mechanisms originating in either the heart or skeletal muscle, we examined cardiac and muscle function and also utilized tissue‐specific KOs in the heart and skeletal muscle. Skeletal muscle mitochondrial function (Yamamoto et al ., 2011), mitochondrial biogenesis (Irrcher et al ., 2003), and resistance to oxidative stress (Nishiyama et al ., 1998; Fisher‐Wellman et al ., 2009; Ryan et al ., 2010) were also examined, as these mechanisms mediate exercise performance (Rockl et al ., 2007). The SIRT1, FOXO3a, and MEK pathways, key to mitochondrial biogenesis and protection against oxidative stress, were also examined (Wu et al ., 1999; Lagouge et al ., 2006; Gurd et al ., 2009; Menzies et al ., 2013; Li et al ., 2015; Smith et al ., 2015).…”

Section: Introductionmentioning

confidence: 99%

Type 5 adenylyl cyclase disruption leads to enhanced exercise performance

et al. 2015

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SummaryThe most important physiological mechanism mediating enhanced exercise performance is increased sympathetic, beta adrenergic receptor (β‐AR), and adenylyl cyclase (AC) activity. This is the first report of decreased AC activity mediating increased exercise performance. We demonstrated that AC5 disruption, that is, knock out (KO) mice, a longevity model, increases exercise performance. Importantly for its relation to longevity, exercise was also improved in old AC5 KO. The mechanism resided in skeletal muscle rather than in the heart, as confirmed by cardiac‐ and skeletal muscle‐specific AC5 KO's, where exercise performance was no longer improved by the cardiac‐specific AC5 KO, but was by the skeletal muscle‐specific AC5 KO, and there was no difference in cardiac output during exercise in AC5 KO vs. WT. Mitochondrial biogenesis was a major mechanism mediating the enhanced exercise. SIRT1, FoxO3a, MEK, and the anti‐oxidant, MnSOD were upregulated in AC5 KO mice. The improved exercise in the AC5 KO was blocked with either a SIRT1 inhibitor, MEK inhibitor, or by mating the AC5 KO with MnSOD hetero KO mice, confirming the role of SIRT1, MEK, and oxidative stress mechanisms. The Caenorhabditis elegans worm AC5 ortholog, acy‐3 by RNAi, also improved fitness, mitochondrial function, antioxidant defense, and lifespan, attesting to the evolutionary conservation of this pathway. Thus, decreasing sympathetic signaling through loss of AC5 is not only a mechanism to improve exercise performance, but is also a mechanism to improve healthful aging, as exercise also protects against diabetes, obesity, and cardiovascular disease, which all limit healthful aging.

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Oxidative stress is related to exercise intolerance in patients with heart failure

Cited by 122 publications

References 25 publications

Oxidative Stress in Heart Failure: The Role of Mitochondria.

Oxidative Stress in Heart Failure: The Role of Mitochondria.

Limited Exercise Capacity in Heterozygous Manganese Superoxide Dismutase Gene–Knockout Mice

Type 5 adenylyl cyclase disruption leads to enhanced exercise performance

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