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Incubation with sodium nitrite attenuates fatigue development in intact single mouse fibres at physiological P O 2

Journal Contribution - Journal Article

Key points: Dietary nitrate supplementation increases plasma nitrite concentration, which provides an oxygen-independent source of nitric oxide and can delay skeletal muscle fatigue. Nitrate supplementation has been shown to increase myofibre calcium release and force production in mouse skeletal muscle during contractions at a supra-physiological oxygen tension, but it is unclear whether nitrite exposure can delay fatigue development and improve myofibre calcium handling at a near-physiological oxygen tension. Single mouse muscle fibres acutely treated with nitrite had a lower force and cytosolic calcium concentration during single non-fatiguing contractions at a near-physiological oxygen tension. Nitrite treatment delayed fatigue development during repeated fatiguing isometric contractions at near-physiological, but not at supra-physiological, oxygen tension in combination with better maintenance of myofilament calcium sensitivity and sarcoplasmic reticulum calcium pumping. These findings improve understanding of the mechanisms by which increased skeletal muscle nitrite exposure might be ergogenic and imply that this is related to improved calcium handling. Abstract: Dietary nitrate (NO 3) supplementation, which increases plasma nitrite (NO 2) concentration, has been reported to attenuate skeletal muscle fatigue development. Sarcoplasmic reticulum (SR) calcium (Ca 2+) release is enhanced in isolated single skeletal muscle fibres following NO 3 supplementation or NO 2 incubation at a supra-physiological PO2 but it is unclear whether NO 2 incubation can alter Ca 2+ handling and fatigue development at a near-physiological (Formula presented.). We hypothesised that NO 2 treatment would improve Ca 2+ handling and delay fatigue at a physiological (Formula presented.) in intact single mouse skeletal muscle fibres. Each muscle fibre was perfused with Tyrode solution pre-equilibrated with either 20% ((Formula presented.) ∼150 Torr) or 2% O 2 ((Formula presented.) = 15.6 Torr) in the absence and presence of 100 µM NaNO 2. At supra-physiological (Formula presented.) (i.e. 20% O 2), time to fatigue was lowered by 34% with NaNO 2 (control: 257 ± 94 vs. NaNO 2: 159 ± 46 s, Cohen's d = 1.63, P < 0.05), but extended by 21% with NaNO 2 at 2% O 2 (control: 308 ± 217 vs. NaNO 2: 368 ± 242 s, d = 1.14, P < 0.01). During the fatiguing contraction protocol completed with NaNO 2 at 2% O 2, peak cytosolic Ca 2+ concentration ([Ca 2+] c) was not different (P > 0.05) but [Ca 2+] c accumulation between contractions was lower, concomitant with a greater SR Ca 2+ pumping rate (P < 0.05) compared to the control condition. These results demonstrate that increased exposure to NO 2 blunts fatigue development at near-physiological, but not at supra-physiological, (Formula presented.) through enhancing SR Ca 2+ pumping rate in single skeletal muscle fibres. These findings extend our understanding of the mechanisms by which increased NO 2 exposure can mitigate skeletal muscle fatigue development.

Journal: Journal of Physiology
ISSN: 0022-3751
Issue: 22
Volume: 597
Pages: 5429-5443
Number of pages: 15
Publication year:2019