Plasma nitrite reserve and endothelial function in the human forearm circulation.
Attenuation of endothelium-derived nitric oxide (NO) synthesis is a hallmark of endothelial dysfunction. Early detection of this disorder may have therapeutic and prognostic implications. Plasma nitrite mirrors acute and chronic changes in endothelial NO-synthase activity. We hypothesized that local plasma nitrite concentration increases during reactive hyperemia of the forearm, reflecting endothelial function. In healthy subjects (n = 11) plasma nitrite and nitrate were determined at baseline and during reactive hyperemia of the forearm using reductive gas-phase chemiluminescence and flow-injection analysis, respectively. Endothelium-dependent dilation of the brachial artery was measured as flow-mediated dilation (FMD) using high-resolution ultrasound. Results were compared to patients with endothelial dysfunction as defined by reduced FMD (n = 11). Reactive hyperemia of the forearm increased local plasma nitrite concentration from 68 +/- 5 to 126 +/- 13 nmol/L (p < 0.01), whereas in endothelial dysfunction nitrite remained unaffected (116 +/- 12 to 104 +/- 10 nmol/L; n.s.), corresponding to nitrite reserves of 94 +/- 21 and -8 +/- 4%. This was accompanied by a significantly greater increase in brachial artery diameter (FMD: 8.5 +/- 0.4% vs 2.9 +/- 0.5%, for healthy subjects and endothelial dysfunction, respectively; p < 0.001). This observation suggests that nitrite changes reflect endothelial function. Assessment of local plasma nitrite during reactive hyperemia may open new avenues in the diagnosis of vascular function.
Rassaf
Tienush
T
Department of Medicine, Division of Cardiology, University Hospital Aachen, 52074 Aachen, Germany.
Heiss
Christian
C
Hendgen-Cotta
Ulrike
U
Balzer
Jan
J
Matern
Simone
S
Kleinbongard
Petra
P
Lee
Andrew
A
Lauer
Thomas
T
Kelm
Malte
M
D000328:Adult; D001916:Brachial Artery / Q000502:physiology; D016022:Case-Control Studies; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood*
D009566:Nitrates; D009573:Nitrites