title: Nitric oxide synthase-derived plasma nitrite predicts exercise capacity.
abstract: BACKGROUND
  Nitrite is the main oxidation product of nitric oxide (NO) in plasma. It sensitively reflects changes in endothelial NO synthase (eNOS) activity under fasting conditions and serves as an endocrine NO donor, contributing to the regulation of blood flow through reaction with haemoglobin. As NO is necessary to maintain an adequate vascular response to the increased demands of blood flow, it is believed to be important for vasodilation induced by exercise.
  
  
  OBJECTIVE
  To investigate whether the capacity of the vasculature to produce nitrite is associated with exercise performance.
  
  
  METHODS
  With the use of chemiluminescence detection, nitrite concentrations in 55 healthy subjects (mean (SEM) age 40 (2) years; 22 men) were studied before and after an exercise test, and endothelial function was determined by measuring flow-mediated dilation of the brachial artery using high-resolution ultrasound. In a subset of subjects, the NOS inhibitor, N(G)-monomethyl-L-arginine, was applied to elucidate the effect of eNOS on changes in nitrite.
  
  
  RESULTS
  Exercise significantly (p<0.001) increased plasma nitrite from 97 (6) to 125 (8) nM. The relative increase in plasma nitrite was related to flow-mediated dilation (6.1 (0.3)%; r = 0.36; p = 0.01). N(G)-Monomethyl-L-arginine blocked increases in nitrite. Post-exercise nitrite concentration correlated with exercise performance, as determined by maximally reached stress power (r = 0.37; p<0.007), and inversely with age. Multivariate analysis showed that both age and post-exercise nitrite concentration were independent predictors of stress endurance and power.
  
  
  CONCLUSIONS
  The results suggest a role for plasma nitrite in the adaptation of haemodynamics during exercise. An impaired increase in plasma nitrite may limit exercise capacity.
authors.affiliation: Department of Medicine, Division of Cardiology, Pulmonary Diseases and Angiology, University Hospital Aachen, Pauwelsstr 30, 52074 Aachen, Germany. trassaf@ukaachen.de
authors.forename: Tienush
authors.initials: T
authors.lastname: Rassaf
authors.forename: Thomas
authors.initials: T
authors.lastname: Lauer
authors.forename: Christian
authors.initials: C
authors.lastname: Heiss
authors.forename: Jan
authors.initials: J
authors.lastname: Balzer
authors.forename: Sarah
authors.initials: S
authors.lastname: Mangold
authors.forename: Thorsten
authors.initials: T
authors.lastname: Leyendecker
authors.forename: Jessica
authors.initials: J
authors.lastname: Rottler
authors.forename: Christine
authors.initials: C
authors.lastname: Drexhage
authors.forename: Christian
authors.initials: C
authors.lastname: Meyer
authors.forename: Malte
authors.initials: M
authors.lastname: Kelm
mesh_terms: D000328:Adult; D001916:Brachial Artery / Q000502:physiology; D017079:Exercise Tolerance / Q000502:physiology*; D005260:Female; D006801:Humans; D008163:Luminescent Measurements; D008297:Male; D015999:Multivariate Analysis; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D009573:Nitrites / Q000097:blood*; D012680:Sensitivity and Specificity; D014664:Vasodilation / Q000502:physiology*
chemical_list: D009573:Nitrites; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase