Effects of acute nitric oxide precursor intake on peripheral and central fatigue during knee extensions in healthy men

Abstract

New Findings What is the central question of this study?What is the effect of acute NO precursor intake on vascular function, muscle and cerebral oxygenation and peripheral and central neuromuscular fatigue during knee‐extension exercise? What is the main finding and its importance?Acute NO precursor ingestion increases the plasma concentrations of NO precursors (nitrate, arginine and citrulline) and enhances post‐ischaemic vasodilatation, but has no significant effect on muscle and cerebral oxygenation, peripheral and central mechanisms of neuromuscular fatigue and, consequently, does not improve exercise performance. Abstract Nitric oxide (NO) plays an important role in matching blood flow to oxygen demand in the brain and contracting muscles during exercise. Previous studies have shown that increasing NO bioavailability can improve muscle function. The aim of this study was to assess the effect of acute NO precursor intake on muscle and cerebral oxygenation and on peripheral and central neuromuscular fatigue during exercise. In four experimental sessions, 15 healthy men performed a thigh ischaemia–reperfusion test followed by submaximal isometric knee extensions (5 s on–4 s off; 45% of maximal voluntary contraction) until task failure. In each session, subjects drank a nitrate‐rich beetroot juice containing 520 mg nitrate (N), N and citrulline (6 g; N+C), N and arginine (6 g; N+A) or a placebo (PLA). Prefrontal cortex and quadriceps near‐infrared spectroscopy parameters were monitored continuously. Transcranial magnetic stimulation and femoral nerve electrical stimulation were used to assess central and peripheral determinants of fatigue. The post‐ischaemic increase in thigh blood total haemoglobin concentration was larger in N (10.1 ± 3.7 mmol) and N+C (10.9 ± 3.3 mmol) compared with PLA (8.2 ± 2.7 mmol; P < 0.05). Nitric oxide precursors had no significant effect on muscle and cerebral oxygenation or on peripheral and central mechanisms of neuromuscular fatigue during exercise. The total number of knee extensions did not differ between sessions (N, 71.9 ± 33.2; N+A, 73.3 ± 39.4; N+C, 74.6 ± 34.0; PLA, 71.8 ± 39.9; P > 0.05). In contrast to the post‐ischaemic hyperaemic response, NO bioavailability in healthy subjects might not be the limiting factor for tissue perfusion and oxygenation during submaximal knee extensions to task failure.

15N‐labeled dietary nitrate supplementation increases human skeletal muscle nitrate concentration and improves muscle torque production

“…first 18 contractions) was significantly greater for NIT compared to PLA. These results contrast with one study, which reported no significant effect of acute NO 3 − ingestion on indices of central or peripheral fatigue or on time‐to‐task‐failure during intermittent isometric knee extension exercise, 31 but are consistent with another study, which found that 5 days of NO 3 − supplementation reduced the rate of muscle fatigue development and extended the time‐to‐task‐failure during dynamic knee extension exercise 32 . Recent meta‐analyses have highlighted the potential for dietary NO 3 − supplementation to enhance skeletal muscle force or power production during high‐intensity exercise 33,34 .…”

Supplementation with Nitric Oxide Precursors for Strength Performance: A Review of the Current Literature

“…Since L-citrulline and nitrates can increase NO via distinct parallel pathways, their combination may also work synergistically. Several studies by Le Roux-Mallouf and colleagues have examined the effect of the combination of BRJ/nitrates and L-citrulline on markers of blood flow (i.e., an ischemia-reperfusion test) with some showing an increase in the post-occlusive hemoglobin/oxyhemoglobin response suggesting enhanced vasodilation [ 116 , 117 ] and others showing no effect [ 118 , 119 ]. However, the one study from this group examining the potential synergistic effect showed that BRJ plus L-citrulline was no better than BRJ in isolation for enhancing the thigh ischemia-reperfusion test [ 117 ].…”

“…Several studies by Le Roux-Mallouf and colleagues have examined the effect of the combination of BRJ/nitrates and L-citrulline on markers of blood flow (i.e., an ischemia-reperfusion test) with some showing an increase in the post-occlusive hemoglobin/oxyhemoglobin response suggesting enhanced vasodilation [ 116 , 117 ] and others showing no effect [ 118 , 119 ]. However, the one study from this group examining the potential synergistic effect showed that BRJ plus L-citrulline was no better than BRJ in isolation for enhancing the thigh ischemia-reperfusion test [ 117 ]. Studies by Le Roux-Mallouf and colleagues also failed to show a significant benefit of the BRJ (520 mg nitrate)/L-citrulline (6 g) combination on isometric knee extension performance [ 117 , 118 ], with the exception of one showing an improvement in maximal knee extensor strength and a trend ( p < 0.10) towards significance in knee extension endurance [ 119 ].…”

“…However, the one study from this group examining the potential synergistic effect showed that BRJ plus L-citrulline was no better than BRJ in isolation for enhancing the thigh ischemia-reperfusion test [ 117 ]. Studies by Le Roux-Mallouf and colleagues also failed to show a significant benefit of the BRJ (520 mg nitrate)/L-citrulline (6 g) combination on isometric knee extension performance [ 117 , 118 ], with the exception of one showing an improvement in maximal knee extensor strength and a trend ( p < 0.10) towards significance in knee extension endurance [ 119 ]. Lastly, a recent study by Burgos et al [ 120 ] failed to show significant improvements in horizontal jump, handgrip strength, and abdominal endurance performance following 9 weeks of supplementing with 3 g L-citrulline, 300 mg nitrates, or a combination.…”

A validated reduced-order dynamic model of nitric oxide regulation in coronary arteries

“…The release of NO is of great importance in the human coronary artery since it helps to provide myocardial oxygen demand of the heart during exercise and cardiac pacing [6]. Besides, it prevents cardiovascular diseases such as atherosclerosis and platelet adhesion and aggregation [7,8].…”