Nitrite Infusion Does Not Alter Isolated Canine Muscle Oxidative Metabolism In Situ During Hypoxia With Normal Convective O2 Delivery

• DOI: 10.1096/fasebj.31.1_supplement.710.11
• Publication Date: 2023-11-26T17:22:04Z
• Authors: Simone Porcelli; Letizia Rasica; Brian S. Ferguson; Andreas N. Kavazis; James R. McDonald; Francesca Mowry; Michael C. Hogan; Bruno Grassi; Bruce L. Gladden

IntroductionPrevious studies have shown a decreased muscle oxygen consumption (V′O2) during moderate intensity exercise in hypoxia after augmented nitric oxide (NO) bioavailability, which suggests an increased efficiency of oxidative metabolism. It is not clear if these effects are related to an NO‐induced increase in convective O2 delivery and/or to an enhanced mitochondrial coupling efficiency. The aim of this study was to examine skeletal muscle contraction economy during hypoxic exercise following nitrite infusion with unchanged convective O2 delivery.MethodsCanine gastrocnemius muscles (n=8) were surgically isolated and electrically stimulated via the sciatic nerve, eliciting 1 contraction every 3 seconds (≈35% V′O2peak) for 3 minutes in hypoxic conditions (PaO2=42±3 mmHg). During contractions, sodium nitrite (NITR) or sodium chloride (SAL) was infused into the popliteal artery. Muscle blood flow was kept constant by a perfusion pump. Muscle force was measured and muscle V′O2 was calculated from the Fick principle. Muscle biopsies were obtained before and after NITR and were used to isolate mitochondria. Mitochondrial respiration rates were recorded by high‐resolution respirometry.ResultsMuscle V′O2 was not significantly different between NITR (60.6±18.0 ml/kg/min) and SAL (61.7±18.3ml/kg/min). After normalizing V′O2 per unit of developed force, the values were slightly but not significantly higher in NITR vs. SAL (p=0.10). No differences were found for ADP‐stimulated mitochondrial respiration (both for complex I and complex II), leak respiration and oxidative phosphorylation coupling.ConclusionIn hypoxic conditions, but in the presence of constant and normal convective O2 delivery, nitrite infusion did not affect canine skeletal muscle oxidative metabolism. These results suggest that the effects of increased NO availability on muscle contraction efficiency in hypoxia, if present, are likely not attributable to changes in mitochondrial respiratory function.