title: Plasma nitroso compounds are decreased in patients with endothelial dysfunction.
abstract: OBJECTIVE
  We investigated whether plasma nitros(yl)ated species (RXNOs) that mediate systemic nitric oxide (NO) bioactivity are depleted in individuals with cardiovascular risk factors and endothelial dysfunction.
  
  
  BACKGROUND
  Endothelium-derived NO acts not only as a regional messenger but exerts significant systemic effects via formation of circulating RXNOs delivering NO to sites of impaired production.
  
  
  METHODS
  Endothelial function was assessed in 68 patients with one to four major cardiovascular risk factors (RF) and 39 healthy control subjects (C) by measurement of flow-mediated dilation (FMD) of the brachial artery using high-resolution ultrasound. In parallel, plasma RXNOs were determined by reductive gas phase chemiluminescence.
  
  
  RESULTS
  Increasing numbers of risk factors were accompanied by a progressive decrease in FMD: 6.5 +/- 0.4% (C); 4.7 +/- 0.5% (one RF); 2.8 +/- 0.4% (two RF); 2.2 +/- 0.4% (three RF); and 1.0 +/- 0.3% (four RF). Progressively impaired vascular function was associated with a concomitant decrease in plasma RXNOs (p < 0.01): 39 +/- 2 nmol/l (C); 30 +/- 2 nmol/l (one RF); 24 +/- 3 nmol/l (two RF); 22 +/- 3 nmol/l (three RF); and 15 +/- 2 nmol/l (four RF), with univariate correlation between FMD and RXNO (r = 0.41, p < 0.001). In a multivariate regression model, RXNO was an independent predictor of endothelial function.
  
  
  CONCLUSIONS
  Endothelial dysfunction in patients with cardiovascular risk factors is associated with decreased levels of circulating RXNOs. Plasma RXNOs may be diagnostically useful markers of NO bioavailability and a surrogate index of endothelial function. Whether the observed decrease in concentration reflects impaired NO formation, accelerated decomposition, and/or consumption of RXNOs and whether these processes play a causal role in the pathophysiology of arteriosclerosis remain to be investigated.
authors.affiliation: Department of Cardiology, Pneumology, and Vascular Medicine, RWTH Aachen, Aachen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Heiss
authors.forename: Thomas
authors.initials: T
authors.lastname: Lauer
authors.forename: André
authors.initials: A
authors.lastname: Dejam
authors.forename: Petra
authors.initials: P
authors.lastname: Kleinbongard
authors.forename: Sandra
authors.initials: S
authors.lastname: Hamada
authors.forename: Tienush
authors.initials: T
authors.lastname: Rassaf
authors.forename: Simone
authors.initials: S
authors.lastname: Matern
authors.forename: Martin
authors.initials: M
authors.lastname: Feelisch
authors.forename: Malte
authors.initials: M
authors.lastname: Kelm
mesh_terms: D000328:Adult; D000368:Aged; D001161:Arteriosclerosis / Q000097:blood / Q000503:physiopathology*; D001783:Blood Flow Velocity; D001916:Brachial Artery / Q000503:physiopathology; D002318:Cardiovascular Diseases / Q000097:blood* / Q000209:etiology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood*; D009573:Nitrites / Q000097:blood; D009603:Nitroso Compounds / Q000097:blood*; D014664:Vasodilation
chemical_list: D009573:Nitrites; D009603:Nitroso Compounds; D009569:Nitric Oxide