Role of nitric oxide in skeletal muscle: synthesis, distribution and functional importance

Reid, Michael B.

doi:10.1046/j.1365-201x.1998.0303f.x

Cited by 222 publications

(206 citation statements)

References 59 publications

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“…NO is a weak reducing agent, with a relatively long half‐life70 and reacts with O 2 to form nitric dioxide and superoxide to produce peroxynitrite 110. There are three different isoforms of NOS expressed in skeletal muscle; the neuronal NOS (nNOS or type I), the inducible NOS (iNOS or type II) and the endothelial NOS isoenzyme (eNOS or type III) 46, 111. nNOS, originally discovered in neuronal tissue, is expressed along the sarcolemma of skeletal muscle fibres and interacts with the dystrophin–glycoprotein complex via a linkage to α1‐syntrophin 112.…”

Section: Chemistry Of Reactive Oxygen and Nitrogen Species Produced Bmentioning

confidence: 99%

Redox homeostasis and age‐related deficits in neuromuscular integrity and function

Sakellariou

Lightfoot

Earl

et al. 2017

J cachexia sarcopenia muscle

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Skeletal muscle is a major site of metabolic activity and is the most abundant tissue in the human body. Age‐related muscle atrophy (sarcopenia) and weakness, characterized by progressive loss of lean muscle mass and function, is a major contributor to morbidity and has a profound effect on the quality of life of older people. With a continuously growing older population (estimated 2 billion of people aged >60 by 2050), demand for medical and social care due to functional deficits, associated with neuromuscular ageing, will inevitably increase. Despite the importance of this ‘epidemic’ problem, the primary biochemical and molecular mechanisms underlying age‐related deficits in neuromuscular integrity and function have not been fully determined. Skeletal muscle generates reactive oxygen and nitrogen species (RONS) from a variety of subcellular sources, and age‐associated oxidative damage has been suggested to be a major factor contributing to the initiation and progression of muscle atrophy inherent with ageing. RONS can modulate a variety of intracellular signal transduction processes, and disruption of these events over time due to altered redox control has been proposed as an underlying mechanism of ageing. The role of oxidants in ageing has been extensively examined in different model organisms that have undergone genetic manipulations with inconsistent findings. Transgenic and knockout rodent studies have provided insight into the function of RONS regulatory systems in neuromuscular ageing. This review summarizes almost 30 years of research in the field of redox homeostasis and muscle ageing, providing a detailed discussion of the experimental approaches that have been undertaken in murine models to examine the role of redox regulation in age‐related muscle atrophy and weakness.

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Section: Chemistry Of Reactive Oxygen and Nitrogen Species Produced Bmentioning

confidence: 99%

Redox homeostasis and age‐related deficits in neuromuscular integrity and function

Sakellariou

Lightfoot

Earl

et al. 2017

J cachexia sarcopenia muscle

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“…A possible explanation for this threshold might be a NO-dependent reduction in skeletal muscle force via modulation of excitation-contraction coupling. It has been reported that the opening of the Ca 2ϩ release channels of the sarcoplasmic reticulum (SR) is inhibited by NO (32,35) and highly related to NO availability (35). In addition, Ca 2ϩ transport (35), SR Ca 2ϩ -ATPase activity (18), and cytochrome c-oxidase inhibition (9) may be influenced by NO and contribute to a dose-dependent modulation of excitation-contraction coupling.…”

Section: Dose Response: Severe-intensity Exercisementioning

confidence: 99%

“…It has been reported that the opening of the Ca 2ϩ release channels of the sarcoplasmic reticulum (SR) is inhibited by NO (32,35) and highly related to NO availability (35). In addition, Ca 2ϩ transport (35), SR Ca 2ϩ -ATPase activity (18), and cytochrome c-oxidase inhibition (9) may be influenced by NO and contribute to a dose-dependent modulation of excitation-contraction coupling. Therefore, whereas an increase in NO bioavailability may result in a more efficient mitochondrial function (24) and changes to type II fiber contractility (17) and blood flow (14), it is possible that these positive effects may be offset by impairments of mitochondrial or contractile function at higher NO levels that might promote nitrative stress.…”

Section: Dose Response: Severe-intensity Exercisementioning

confidence: 99%

“…Although the mechanism(s) responsible for the ergogenic potential of NO 3 Ϫ supplementation remain uncertain, they are believed to be mediated via a biochemical reduction of ingested NO 3 Ϫ to biologically active NO 2 Ϫ and NO (4). NO has been linked to the efficiency of aerobic respiration (9) and the regulation of muscle contraction (35). Indeed, both more efficient mitochondrial oxidative phosphorylation, via a reduced proton leak across the inner mitochondrial membrane (24) and a reduced ATP and phosphocreatine cost of muscle force production (2,15), has been reported following dietary NO 3 Ϫ supplementation.…”

Section: Dose Response: Severe-intensity Exercisementioning

confidence: 99%

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Beetroot juice and exercise: pharmacodynamic and dose-response relationships

Wylie

Kelly

Bailey

et al. 2013

Journal of Applied Physiology

414

449

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Ϫ ] increased in a dose-dependent manner, with the peak changes occurring at approximately 2-3 h. Compared with PL, 70 ml BR did not alter the physiological responses to exercise. However, 140 and 280 ml BR reduced the steady-state oxygen (O2) uptake during moderateintensity exercise by 1.7% (P ϭ 0.06) and 3.0% (P Ͻ 0.05), whereas time-to-task failure was extended by 14% and 12% (both P Ͻ 0.05), respectively, compared with PL. The results indicate that whereas plasma [NO 2 Ϫ ] and the O2 cost of moderate-intensity exercise are altered dose dependently with NO 3 Ϫ -rich BR, there is no additional improvement in exercise tolerance after ingesting BR containing 16.8 compared with 8.4 mmol NO 3 Ϫ . These findings have important implications for the use of BR to enhance cardiovascular health and exercise performance in young adults.nitrate; nitrite; nitric oxide; blood pressure; exercise economy; O2 uptake; exercise tolerance NITRIC OXIDE (NO) IS A GASEOUS signaling molecule that modulates human physiological function via its role in, for example, the regulation of blood flow, neurotransmission, immune function, glucose and calcium homeostasis, muscle contractility, and mitochondrial respiration (9, 36). 1 NO is generated through the oxidation of the amino acid L-arginine Ϫ ] peaked 3 h postingestion, remained close to peak values until 5 h postingestion, and returned to baseline after 24 h (39). The systolic and diastolic BP and the mean arterial pressure (MAP) were reduced significantly, by ϳ10, ϳ8, and ϳ8 mmHg, respectively, at 2.5-3 h after BR intake. The same research group later reported a dose-dependent increase in plasma [ ] was accompanied by significant reductions in both systolic BP (of ϳ2, ϳ6, and ϳ9 mmHg, respectively) and diastolic BP (of ϳ4, ϳ4, and ϳ6 mmHg, respectively). However, since BR contains polyphenols and antioxidants, which can facilitate the synthesis of NO from NO 2 Ϫ in the stomach (30), it is unclear whether BP is similarly impacted when different doses of BR are ingested compared with equivalent doses of NO 3 Ϫ salts. Given the growing interest in dietary NO 3 Ϫ supplementation in the form of BR amongst athletes and the general population, it is important to determine the pharmacokinetic-pharmacodynamic relationship between different volumes of BR consumption and changes in plasma [NO 2 Ϫ ] and BP to establish an optimal dose for beneficial effects.Recent investigations suggest that dietary NO 3 Ϫ supplementation has the potential to influence human physiology beyond 1 This article is the topic of an Invited Editorial by L. Burke (5a).

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“…Biological activities of NO and ROS are strongly interdependent (28,43). They and their redox derivatives compete for the same metal centers and thiol groups on the target protein (1,43).…”

Section: Effects Of No On Isotonic Contractile and Fatigue Propertiesmentioning

confidence: 99%

Effects of modulation of nitric oxide on rat diaphragm isotonic contractility during hypoxia

Zhu

Heunks

Machiels

et al. 2003

Journal of Applied Physiology

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Effects of modulation of nitric oxide on rat diaphragm isotonic contractility during hypoxia. J Appl Physiol 94: 612-620, 2003. First published October 18, 2002 10.1152/ japplphysiol.00441.2002 is essential for optimal myofilament function of the rat diaphragm in vitro during active shortening. Little is known about the role of NO in muscle contraction under hypoxic conditions. Hypoxia might increase the NO synthase (NOS) activity within the rat diaphragm. We hypothesized that NO plays a protective role in isotonic contractile and fatigue properties during hypoxia in vitro. The effects of the NOS inhibitor N G -monomethyl-L-arginine (L-NMMA), the NO scavenger hemoglobin, and the NO donor spermine NONOate on shortening velocity, power generation, and isotonic fatigability during hypoxia were evaluated (PO 2 ϳ 7 kPa). L-NMMA and hemoglobin slowed the shortening velocity, depressed power generation, and increased isotonic fatigability during hypoxia. The effects of L-NMMA were prevented by coadministration with the NOS substrate L-arginine. Spermine NONOate did not alter isotonic contractile and fatigue properties during hypoxia. These results indicate that endogenous NO is needed for optimal muscle contraction of the rat diaphragm in vitro during hypoxia.N G -monomethyl-L-arginine; hemoglobin; spermine NONOate SKELETAL MUSCLE, INCLUDING the diaphragm, continuously produces nitric oxide (NO) (3,26). NO is produced in biological systems via the enzymatic action of NO synthase (NOS) (32). NO generation by the constitutive NOS isoforms (neuronal NOS and endothelial NOS) is calcium dependent (16). NO production within skeletal muscle is enhanced during contractile activity (5).NO has been shown to modulate contractile properties of skeletal muscle in vitro. The overall effect depends on the experimental paradigm. Inhibition of NOS increases twitch and submaximal tetanic force of the rat diaphragm. These alterations are reversed by NO donors (26), suggesting that NO inhibits excitation-contraction coupling in unfatigued muscle. On the other hand, NO is essential for optimal myofilament function in the rat diaphragm during active shortening in vitro (36). Inhibition of NOS decreases the shortening velocity and power generation of the rat diaphragm under hyperoxic conditions (36). These findings of NOS inhibition on force generation and velocity of shortening indicate multiple possible targets for NO in skeletal muscle. In fatiguing contractions, supplementation with exogenous NO slowed the decline of maximal force in mouse soleus muscle (38). This finding suggests that NO preserves skeletal muscle function in vitro during strenuous contractile activity.Hypoxia impairs force generation and accelerates skeletal muscle fatigue in vitro (21, 48). To date, no study has investigated the role of NO in shortening velocity or isotonic fatigability during hypoxia. This is of particular interest because NO affects excitationcontraction coupling in striated muscle (26), and O 2 tension is an important factor in regulating NOS in an...

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Role of nitric oxide in skeletal muscle: synthesis, distribution and functional importance

Cited by 222 publications

References 59 publications

Redox homeostasis and age‐related deficits in neuromuscular integrity and function

Redox homeostasis and age‐related deficits in neuromuscular integrity and function

Beetroot juice and exercise: pharmacodynamic and dose-response relationships

Effects of modulation of nitric oxide on rat diaphragm isotonic contractility during hypoxia

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