title: Plasma nitrite concentrations reflect the degree of endothelial dysfunction in humans.
abstract: A reduced nitric oxide availability is a hallmark of endothelial dysfunction occurring early in atherosclerosis. Recently, we have shown that plasma nitrite mirrors acute changes in endothelial nitric oxide synthase activity in various mammals, including humans. Here, we examined the hypothesis that plasma nitrite levels are reduced in humans with endothelial dysfunction and the decrease is correlated with increasing numbers of cardiovascular risk factors (RF). Plasma nitrite concentrations were quantified by flow-injection analysis. The coefficient of variation for repeated measurements of plasma nitrite was <8%, and heart rate and blood pressure at the time of blood sampling had no significant effect on nitrite values measured (n=10). Baseline levels of plasma nitrite followed a normal distribution in each group studied and decreased progressively with increasing numbers of cardiovascular risk factors (n=351, p<0.001): 351+/-13 (0 RF), 261+/-10 (1 RF), 253+/-11 (2 RF), 222+/-18 (3 RF), and 171+/-29 nmol/L (4 RF). Intima media thickness (IMT) and flow-mediated dilation (FMD) were determined via ultrasound. Plasma nitrite and FMD levels were lower, whereas IMT was greater in individuals with endothelial dysfunction (n=12) compared to healthy volunteers (n=12). Nitrite correlated significantly with FMD (r=0.56, p<0.001) and inversely with IMT (r= -0.49, p<0.01). Plasma nitrite levels are reliably measurable in humans, indicate endothelial dysfunction, and correlate with cardiovascular risk factors. Future studies are necessary to identify the prognostic relevance of plasma nitrite determination in patients suffering from cardiovascular disease.
authors.affiliation: Division of Cardiology, Pulmonary Diseases and Angiology, Department of Medicine, Heinrich Heine University, D-40225 Düsseldorf, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Kleinbongard
authors.forename: André
authors.initials: A
authors.lastname: Dejam
authors.forename: Thomas
authors.initials: T
authors.lastname: Lauer
authors.forename: Thomas
authors.initials: T
authors.lastname: Jax
authors.forename: Stefan
authors.initials: S
authors.lastname: Kerber
authors.forename: Putrika
authors.initials: P
authors.lastname: Gharini
authors.forename: Jan
authors.initials: J
authors.lastname: Balzer
authors.forename: Rainer B
authors.initials: RB
authors.lastname: Zotz
authors.forename: Rüdiger E
authors.initials: RE
authors.lastname: Scharf
authors.forename: Reinhart
authors.initials: R
authors.lastname: Willers
authors.forename: Alan N
authors.initials: AN
authors.lastname: Schechter
authors.forename: Martin
authors.initials: M
authors.lastname: Feelisch
authors.forename: Malte
authors.initials: M
authors.lastname: Kelm
mesh_terms: D000328:Adult; D002318:Cardiovascular Diseases / Q000097:blood / Q000175:diagnosis* / Q000503:physiopathology*; D003430:Cross-Sectional Studies; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood*; D012044:Regression Analysis; D015203:Reproducibility of Results; D012307:Risk Factors; D014664:Vasodilation / Q000187:drug effects
chemical_list: D009566:Nitrates; D009573:Nitrites