Nitrite Concentration in the Striated Muscles Is Reversely Related to Myoglobin and Mitochondrial Proteins Content in Rats

Majerczak, Joanna; Kij, Agnieszka; Drzymała‐Celichowska, Hanna; Kuś, Kamil; Karasiński, J; Nieckarz, Zenon; Grandys, Marcin; Celichowski, Jan; Szkutnik, Zbigniew; Hendgen‐Cotta, Ulrike B.; Żołądź, Jerzy A.

doi:10.3390/ijms23052686

Cited by 8 publications

(20 citation statements)

References 66 publications

(136 reference statements)

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“…Therefore, specific effects of ingested NO 3 − on Ca 2+ handling and contractility in type II muscle fibers 47 might be hypothesized to play a role in the improved torque generation we observed in NIT compared to PLA over the first 90 s of the exercise test. This hypothesis would also be consistent with a recent report that fast‐twitch muscle has a greater [NO 2 − ] than slow‐twitch muscle 48 . Practically, our results suggest that athletes competing in sports which require maximal rates of force production and acceleration from the start to overcome inertia or for tactical advantage may benefit from dietary NO 3 − supplementation.…”

Section: Discussionsupporting

confidence: 92%

“…This hypothesis would also be consistent with a recent report that fast-twitch muscle has a greater [NO 2 − ] than slow-twitch muscle. 48 Practically, our results suggest that athletes competing in sports which require maximal rates of force production and acceleration from the start to overcome inertia or for tactical advantage may benefit from dietary NO 3 − supplementation. However, the increased capacity for force generation afforded by NO 3 − ingestion may also be beneficial in continuous or intermittent high-intensity activities in which physical effort is more evenly distributed.…”

Section: Exercise Performancementioning

confidence: 71%

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¹⁵N‐labeled dietary nitrate supplementation increases human skeletal muscle nitrate concentration and improves muscle torque production

et al. 2023

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Aim Dietary nitrate (NO3−) supplementation increases nitric oxide bioavailability and can enhance exercise performance. We investigated the distribution and metabolic fate of ingested NO3− at rest and during exercise with a focus on skeletal muscle. Methods In a randomized, crossover study, 10 healthy volunteers consumed 12.8 mmol 15N‐labeled potassium nitrate (K15NO3; NIT) or potassium chloride placebo (PLA). Muscle biopsies were taken at baseline, at 1‐ and 3‐h post‐supplement ingestion, and immediately following the completion of 60 maximal intermittent contractions of the knee extensors. Muscle, plasma, saliva, and urine samples were analyzed using chemiluminescence to determine absolute [NO3−] and [NO2−], and by mass spectrometry to determine the proportion of NO3− and NO2− that was 15N‐labeled. Results Neither muscle [NO3−] nor [NO2−] were altered by PLA. Following NIT, muscle [NO3−] (but not [NO2−]) was elevated at 1‐h (from ~35 to 147 nmol/g, p < 0.001) and 3‐h, with almost all of the increase being 15N‐labeled. There was a significant reduction in 15N‐labeled muscle [NO3−] from pre‐ to post‐exercise. Relative to PLA, mean muscle torque production was ~7% greater during the first 18 contractions following NIT. This improvement in torque was correlated with the pre‐exercise 15N‐labeled muscle [NO3−] and the magnitude of decline in 15N‐labeled muscle [NO3−] during exercise (r = 0.66 and r = 0.62, respectively; p < 0.01). Conclusion This study shows, for the first time, that skeletal muscle rapidly takes up dietary NO3−, the elevated muscle [NO3−] following NO3− ingestion declines during exercise, and muscle NO3− dynamics are associated with enhanced torque production during maximal intermittent muscle contractions.

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Section: Discussionsupporting

confidence: 92%

Section: Exercise Performancementioning

confidence: 71%

¹⁵N‐labeled dietary nitrate supplementation increases human skeletal muscle nitrate concentration and improves muscle torque production

et al. 2023

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“…Levels of NO • metabolites including NO 2 − and NO 3 − in plasma and in the muscle homogenates (heart ventricles and locomotory muscles, i.e. the gastrocnemius and tibialis anterior) were determined by a liquid chromatography‐based method with post‐column derivatization using an ENO‐20‐NO x analyser (Eicom Corp., San Diego, CA, USA), as previously described (Kij et al., 2021; Majerczak et al., 2022; Przyborowski et al., 2018). Briefly, the plasma samples were subjected to protein precipitation using methanol, and after centrifugation the clean supernatant was injected into an HPLC system.…”

Section: Methodsmentioning

confidence: 99%

Myoglobin deficiency impairs maximal oxygen uptake and exercise performance: a lesson from Mb^−/− mice

Zoladz,

Grandys,

Smeda

et al. 2024

The Journal of Physiology

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Myoglobin (Mb) plays an important role at rest and during exercise as a reservoir of oxygen and has been suggested to regulate NO• bioavailability under hypoxic/acidic conditions. However, its ultimate role during exercise is still a subject of debate. We aimed to study the effect of Mb deficiency on maximal oxygen uptake () and exercise performance in myoglobin knockout mice (Mb−/−) when compared to control mice (Mb+/+). Furthermore, we also studied NO• bioavailability, assessed as nitrite (NO2−) and nitrate (NO3−) in the heart, locomotory muscle and in plasma, at rest and during exercise at exhaustion both in Mb−/− and in Mb+/+ mice. The mice performed maximal running incremental exercise on a treadmill with whole‐body gas exchange measurements. The Mb−/− mice had lower body mass, heart and hind limb muscle mass (P < 0.001). Mb−/− mice had significantly reduced maximal running performance (P < 0.001). expressed in ml min−1 in Mb−/− mice was 37% lower than in Mb+/+ mice (P < 0.001) and 13% lower when expressed in ml min−1 kg body mass−1 (P = 0.001). Additionally, Mb−/− mice had significantly lower plasma, heart and locomotory muscle NO2− levels at rest. During exercise NO2− increased significantly in the heart and locomotory muscles of Mb−/− and Mb+/+ mice, whereas no significant changes in NO2− were found in plasma. Our study showed that, contrary to recent suggestions, Mb deficiency significantly impairs and maximal running performance in mice. imageKey points Myoglobin knockout mice (Mb−/−) possess lower maximal oxygen uptake () and poorer maximal running performance than control mice (Mb+/+). Respiratory exchange ratio values at high running velocities in Mb−/− mice are higher than in control mice suggesting a shift in substrate utilization towards glucose metabolism in Mb−/− mice at the same running velocities. Lack of myoglobin lowers basal systemic and muscle NO• bioavailability, but does not affect exercise‐induced NO2− changes in plasma, heart and locomotory muscles. The present study demonstrates that myoglobin is of vital importance for and maximal running performance as well as explains why previous studies have failed to prove such a role of myoglobin when using the Mb−/− mouse model.

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“…Проте він є нестійкою сполукою, оскільки його період напівжиття складає кілька хвилин та залежить від багатьох умов (парціального тиску кисню у тканині, температури, концентрації самого оксиду азоту, джерела його утворення, тощо). За умов температури людського організму (≈37°С) та фізіологічної концентрації кисню у тканинах оксид азоту легко піддається оксисненню з утворенням нітритів (NO2 -) [8]. Окиснення оксиду азоту молекулярним киснем не завершується з утворенням нітритів.…”

Section: результати та їх обговоренняunclassified

“…Окиснення оксиду азоту молекулярним киснем не завершується з утворенням нітритів. В подальшому за тих самих умов відбувається окиснення нітритів до нітратів (NO3 -), надлишок яких може виводяться нирками, або зберігатись у скелетних м'язах для подальшого відновлення до оксиду азоту (NO) [8]. Тому за фізіологічних умов окиснення NO до нітритів можна розглядати як безпечний шлях утилізації надлишкового NO.…”

Section: результати та їх обговоренняunclassified

The Role of Ap-1 Transcription Factor Activation in the Changes of Production and Utilization of Nitric Oxide in the Gastric Mucosa of Rats Under Conditions of Chronic Fluoride Intoxication

Акімов¹

2022

Med. and Ecol. probl.

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Millions of people are affected by excessive fluoride intake. The effect of fluorides on the activation or inhibition of redox-sensitive transcription factors remains poorly understood. The aim of this research is to examine the effect of activation of the transcription factor AP-1 on changes in the activity of inducible NO synthase and constitutive isoforms of NO synthase, concentrations of peroxynitrites of alkali and alkaline earth metals, concentrations of nitrites and nitrosothiols in the gastric mucosa of rats under conditions of chronic fluoride intoxication. The study was conducted on 18 adult male Wistar rats weighing 220-260 g. Experimental animals were randomly divided into 3 groups of 6 animals each: control, chronic fluoride intoxication group and AP-1 transcription factor blockade group. Chronic fluoride intoxication was simulated by the administration of sodium fluoride at a dose of 10 mg / kg for 30 days. AP-1 blockade was performed by administering SR11302 at a rate of 15 mg / kg twice a week. In the gastric mucosa, the following was studied: the activities of constitutive and inducible isoforms of NO synthase, the concentration of nitrites, peroxynitrites and nitrosothiols. Chronic fluoride intoxication reduces the activity of constitutive NO synthases by 37.73% and increases the activity of inducible NO synthase by 1.61 times. The concentration of peroxynitrites increases by 2.68 times, nitrites – by 1.74 times, and nitrosothiols – by 1.88 times. Blockade of AP-1 reduces the activity of inducible isoform by 2.11, does not affect the activity of constitutive isoforms, and reduces the concentration of peroxynitrites by 1.98 times, nitrites – by 2.10 times, and nitrosothiols – by 2.37 times. Activation of the transcription factor AP-1 under conditions of chronic excessive fluoride intake leads to increased production of nitric oxide in the gastric mucosa of rats, enhances its oxidation to nitrites, promotes the formation of nitrosyl groups in the reaction with low molecular weight donors of thiol groups and increases the peroxidation of nitric oxide with the formation of peroxynitrite.

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Nitrite Concentration in the Striated Muscles Is Reversely Related to Myoglobin and Mitochondrial Proteins Content in Rats

Cited by 8 publications

References 66 publications

¹⁵N‐labeled dietary nitrate supplementation increases human skeletal muscle nitrate concentration and improves muscle torque production

¹⁵N‐labeled dietary nitrate supplementation increases human skeletal muscle nitrate concentration and improves muscle torque production

Myoglobin deficiency impairs maximal oxygen uptake and exercise performance: a lesson from Mb^−/− mice

The Role of Ap-1 Transcription Factor Activation in the Changes of Production and Utilization of Nitric Oxide in the Gastric Mucosa of Rats Under Conditions of Chronic Fluoride Intoxication

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Nitrite Concentration in the Striated Muscles Is Reversely Related to Myoglobin and Mitochondrial Proteins Content in Rats

Cited by 8 publications

References 66 publications

15N‐labeled dietary nitrate supplementation increases human skeletal muscle nitrate concentration and improves muscle torque production

15N‐labeled dietary nitrate supplementation increases human skeletal muscle nitrate concentration and improves muscle torque production

Myoglobin deficiency impairs maximal oxygen uptake and exercise performance: a lesson from Mb−/− mice

The Role of Ap-1 Transcription Factor Activation in the Changes of Production and Utilization of Nitric Oxide in the Gastric Mucosa of Rats Under Conditions of Chronic Fluoride Intoxication

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¹⁵N‐labeled dietary nitrate supplementation increases human skeletal muscle nitrate concentration and improves muscle torque production

¹⁵N‐labeled dietary nitrate supplementation increases human skeletal muscle nitrate concentration and improves muscle torque production

Myoglobin deficiency impairs maximal oxygen uptake and exercise performance: a lesson from Mb^−/− mice