Bailey SJ, Varnham RL, DiMenna FJ, Breese BC, Wylie LJ, Jones AM. Inorganic nitrate supplementation improves muscle oxygenation, O2 uptake kinetics, and exercise tolerance at high but not low pedal rates. J Appl Physiol 118: 1396 -1405, 2015. First published April 9, 2015 doi:10.1152/japplphysiol.01141.2014.-We tested the hypothesis that inorganic nitrate (NO3 Ϫ ) supplementation would improve muscle oxygenation, pulmonary oxygen uptake (V O2) kinetics, and exercise tolerance (Tlim) to a greater extent when cycling at high compared with low pedal rates. In a randomized, placebo-controlled cross-over study, seven subjects (mean Ϯ SD, age 21 Ϯ 2 yr, body mass 86 Ϯ 10 kg) completed severe-intensity step cycle tests at pedal cadences of 35 rpm and 115 rpm during separate nine-day supplementation periods with NO3 Ϫ -rich beetroot juice (BR) (providing 8.4 mmol NO3 Ϫ /day) and placebo (PLA). Compared with PLA, plasma nitrite concentration increased 178% with BR (P Ͻ 0.01). There were no significant differences in muscle oxyhemoglobin concentration ([O2Hb]), phase II V O2 kinetics, or Tlim between BR and PLA when cycling at 35 rpm (P Ͼ 0.05). However, when cycling at 115 rpm, muscle [O2Hb] was higher at baseline and throughout exercise, phase II V O2 kinetics was faster (47 Ϯ 16 s vs. 61 Ϯ 25 s; P Ͻ 0.05), and Tlim was greater (362 Ϯ 137 s vs. 297 Ϯ 79 s; P Ͻ 0.05) with BR compared with PLA. These results suggest that short-term BR supplementation can increase muscle oxygenation, expedite the adjustment of oxidative metabolism, and enhance exercise tolerance when cycling at a high, but not a low, pedal cadence in healthy recreationally active subjects. These findings support recent observations that NO3 Ϫ supplementation may be particularly effective at improving physiological and functional responses in type II muscle fibers. nitric oxide; vascular function; oxidative metabolism; exercise performance; fatigue NITRIC OXIDE (NO) IS A DIFFUSIBLE GAS that impacts a plethora of physiological responses including skeletal muscle perfusion, metabolism, force production, and fatigue resistance (56). It is well documented that NO is produced by the nitric oxide synthase enzymes, which catalyze the complex five-electron oxidation of the semiessential amino acid, L-arginine (10). More recently, there has been a growing appreciation of the potential for NO synthesis from the simple one-electron reduction of nitrite (NO 2 Ϫ ), in a reaction catalyzed by numerous NO 2 Ϫ reductases (44, 57). Importantly, increasing the intake of dietary inorganic nitrate (NO 3 Ϫ ), which passes into the enterosalivary circulation for subsequent reduction to NO 2 Ϫ by oral anaerobes (19), has been shown to positively impact NO biomarkers, exercise efficiency, and exercise tolerance in recreationally active subjects (3,4,12,42,43,58,61). Therefore, supplementation with NO 3 Ϫ appears to represent an effective dietary intervention to improve NO bioavailability, contractile efficiency, and fatigue resistance.Results from in vitro studies suggest that th...