Incubation with sodium nitrite attenuates fatigue development in intact single mouse fibres at physiological PO2

Dietary nitrate (NO3-) supplementation, which increases plasma nitrite (NO2-)concentration, has been reported to attenuates keletal muscle fatigue development. Sarcoplasmic reticulum (SR) calcium (Ca2+)release is enhanced in isolated single skeletal muscle fibres following NO3-supplementation or NO2-incubation at a supra-physiological PO2but it is unclear whether NO2-incubation can alter Ca2+handling and fatigue development at a near-physiological PO2. We hypothesised that NO2-treatment would improve Ca2+handling and delay fatigue at a physiological PO2 in intact single mouse skeletal muscle fibres. Each muscle fibre was perfused with Tyrode’s solution pre-equilibrated with either 20% (PO2~150 Torr) or 2% O2(PO2=15.6 Torr) in the absence and presence of 100 μM NaNO2. At supra-physiological PO2 (i.e., 20% O2), time to fatigue was lowered by 34% with NaNO2 (control: 257 ± 94 vs. NaNO2: 159 ± 46 s, d=1.63, P<0.05), but extended by 21% with NaNO2 at 2% O2 (control: 308 ± 217 vs. NaNO2: 368 ± 242 s, d=1.14, P<0.01). During the fatiguing contraction protocol completed with NaNO2 at 2% O2, peak cytosolic Ca2+concentration ([Ca2+]c) was not different (P>0.05) but [Ca2+] caccumulation between contractions was lower,concomitant with a greater SR Ca2+ pumping rate (P<0.05)compared to the control condition. These results demonstrate that increased exposure to NO2-blunts
fatigue development at near-physiological, but not at supra-physiological,PO2through enhancing SR Ca2+pumping rate in single skeletal muscle fibres. These findings extend our understanding of the mechanisms by which increased NO2-exposure can mitigate skeletal muscle fatigue development.