High doses of sodium nitrate prior to exhaustive exercise increases plasma peroxynitrite levels in well-trained subjects: randomized, double-blinded, crossover study

Abstract

The aim of this study was to investigate the effect of different doses of pre-workout sodium nitrate supplementation on nitric oxide, peroxynitrite levels, and performance parameters. Ten well-trained male subjects participated in a randomized, double-blinded, crossover study. They ingested 8, 16, and 24 mmol sodium nitrate or placebo (NaCl) dissolved in water at 2.5 h before an incremental exercise test. Respiratory gases (oxygen consumption, carbon dioxide production, respiratory exchange ratio) were measured throughout the exercise trials and 3 blood samples (pre-ingestion, 2.5 h post-ingestion and postexercise) were taken to analyze nitrate/nitrite (NOx) and peroxynitrite levels. Data were analyzed using repeated-measures ANOVA at significance level of P < 0.05. NOx levels significantly increased following sodium nitrate ingestion compared with placebo (placebo: 40.86 ± 10.7 μmol/L, 8 mmol: 203.69 ± 25.1 μmol/L, 16 mmol: 289.41 ± 30.1 μmol/L, and 24 mmol: 300.95 ± 42.4 μmol/L, respectively) (P = 0.0001). However, this did not induce any significant change in oxygen consumption (P = 0.351), blood lactate concentration (P = 0.245), and time-to-exhaustion (P = 0.147). Peroxynitrite levels were similar compared with placebo when participants ingested 8 and 16 mmol of inorganic nitrate but a significant increase was observed after exercise at maximal intensity when participants were supplemented with 24 mmol (mean = 14.60 ± 1.3 μmol/L, P = 0.001). Pre-workout ingestion of high dose of sodium nitrate (24 mmol) induced peroxynitrate formation, a marker of oxidative stress. Caution must be taken regarding administration of higher doses before benefits or adverse effects are established in this population.

Effects of different intensities of continuous training on vascular inflammation and oxidative stress in spontaneously hypertensive rats

“…In human studies, it has been confirmed that high‐intensity training increases oxidative stress 41–44 44 which may be involved in the progression of oxidative stress in SHR; our data regarding the detection of 3‐NT in the mesenteric artery further confirmed this conclusion. There are two free radical (FR) defence systems in the human body: an enzymatic defence system involving superoxide dismutase, glutathione peroxidase (GSH‐Px), catalase (CAT) and glutathione reductase (GR), and a non‐enzymatic defence system involving vitamin C, vitamin E and glutathione (GSH).…”

“…HICT causes an increase in the level of vascular oxidative stress, leading to an increase in the ROS‐related uncoupling of eNOS, and the balance between NO and ROS is lost, which in turn causes a vicious cycle of reduced NO bioavailability and increased ROS 42 . In human studies, it has been confirmed that high‐intensity training increases oxidative stress 41–44 44 which may be involved in the progression of oxidative stress in SHR; our data regarding the detection of 3‐NT in the mesenteric artery further confirmed this conclusion.…”

Dose-response effect of dietary nitrate on muscle contractility and blood pressure in older subjects

“…We therefore measured plasma 3-NT concentrations, as another marker of the rate of NO production but also to determine whether the higher dose of NO 3 -(which averaged 28.7±2.7 mmol) resulted in "peaking over" of muscle contractile function due to an increase in nitrosative stress. This possibility was suggested by the recent results of Gholami et al (33), who reported that ingestion of 24, but not 8 or 16, mmol of NO 3 resulted in a dramatic increase in plasma peroxynitrite levels in well-trained subjects following a maximal incremental exercise test. In the present study, however, the pattern of change in plasma 3-NT instead generally resembled that of breath NO, i.e., tending to increase slightly after the lower dose but decrease slightly after the higher dose of NO 3 -.…”

Facilitating Nitrite-Derived S-Nitrosothiol Formation in the Upper Gastrointestinal Tract in the Therapy of Cardiovascular Diseases

“…Superoxide (a major ROS) reacts with NO and generates peroxynitrite (ONOO − ), an important oxidizing agent which causes critical damage to cells. Therefore, increased oxidative stress increases NO consumption and promotes peroxynitrite formation [ 37 ]. BMPRII, in turn, is involved in regulating angiogenesis, and proliferation and survival of endothelial cells.…”