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Key points: We determined if bed rest increased mitochondrially derived reactive oxygen species and cellular redox stress, contributing to the induction of insulin resistance.Bed rest decreased maximal and submaximal ADP‐stimulated mitochondrial respiration.Bed rest did not alter mitochondrial H2O2 emission in the presence of ADP concentrations indicative of resting muscle, the ratio of H2O2 emission to mitochondrial O2 consumption or markers of oxidative stressThe present data suggest strongly that mitochondrial H2O2 does not contribute to bed rest‐induced insulin resistance Mitochondrial H2O2 has been causally linked to diet‐induced insulin resistance, although it remains unclear if muscle disuse similarly increases mitochondrial H2O2. Therefore, we investigated the potential that an increase in skeletal muscle mitochondrial H2O2 emission, potentially as a result of decreased ADP sensitivity, contributes to cellular redox stress and the induction of insulin resistance during short‐term bed rest in 20 healthy males. Bed rest led to a decline in glucose infusion rate during a hyperinsulinaemic‐euglycaemic clamp (−42 ± 2%; P < 0.001), and in permeabilized skeletal muscle fibres it decreased OXPHOS protein content (−16 ± 8%) and mitochondrial respiration across a range of ADP concentrations (−13 ± 5%). While bed rest tended to increase maximal mitochondrial H2O2 emission rates (P = 0.053), H2O2 emission in the presence of ADP concentrations indicative of resting muscle, the ratio of H2O2 emission to mitochondrial O2 consumption, and markers of oxidative stress were not altered following bed rest. Altogether, while bed rest impairs mitochondrial ADP‐stimulated respiration, an increase in mitochondrial H2O2 emission does not contribute to the induction of insulin resistance following short‐term bed rest. Key points: We determined if bed rest increased mitochondrially derived reactive oxygen species and cellular redox stress, contributing to the induction of insulin resistance.Bed rest decreased maximal and submaximal ADP‐stimulated mitochondrial respiration.Bed rest did not alter mitochondrial H2O2 emission in the presence of ADP concentrations indicative of resting muscle, the ratio of H2O2 emission to mitochondrial O2 consumption or markers of oxidative stressThe present data suggest strongly that mitochondrial H2O2 does not contribute to bed rest‐induced insulin resistance [ABSTRACT FROM AUTHOR]

Supplementation with dietary inorganic nitrate (NO3-) is increasingly recognized to confer cardioprotective effects in both healthy and clinical populations. While the mechanism(s) remains ambiguous, in skeletal muscle oral consumption of NaNO3 has been shown to improve mitochondrial efficiency. Whether NaNO3 has similar3 effects on mitochondria within the heart is unknown. Therefore, we comprehensively investigated the effect of NaNO3 supplementation on in vivo left ventricular (LV) function and mitochondrial bioenergetics. Healthy male Sprague-Dawley rats were supplemented with NaNO3 (1 g/l) in their drinking water for 7 days. Echocardiography and invasive hemodynamics were used to assess LV morphology and function. Blood pressure (BP) was measured by tail-cuff and invasive hemodynamics. Mitochondrial bioenergetics were measured in LV isolated mitochondria and permeabilized muscle fibers by high-resolution respirometry and fluorometry. Nitrate decreased (P < 0.05) BP, LV end-diastolic pressure, and maximal LV pressure. Rates of LV relaxation (when normalized to mean arterial pressure) tended (P = 0.13) to be higher with nitrate supplementation. However, nitrate did not alter LV mitochondrial respiration, coupling efficiency, or oxygen affinity in isolated mitochondria or permeabilized muscle fibers. In contrast, nitrate increased (P < 0.05) the propensity for mitochondrial H2O2 emission in the absence of changes in cellular redox state and decreased the sensitivity of mitochondria to ADP (apparent Km). These results add to the therapeutic potential of nitrate supplementation in cardiovascular diseases and suggest that nitrate may confer these beneficial effects via mitochondrial redox signaling. [ABSTRACT FROM AUTHOR]