Plasma nitrite reserve and endothelial function in the human forearm circulation

• Published in: Free radical biology & medicine Vol. 41; no. 2; pp. 295 - 301
• Main Authors: Rassaf, Tienush, Heiss, Christian, Hendgen-Cotta, Ulrike, Balzer, Jan, Matern, Simone, Kleinbongard, Petra, Lee, Andrew, Lauer, Thomas, Kelm, Malte
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.07.2006
• Subjects: Adult; Brachial Artery - physiology; Case-Control Studies; Endothelial function; Endothelium, Vascular - physiology; Female; Forearm - blood supply; Free radical; Humans; Male; Middle Aged; Nitrates - blood; Nitric oxide; Nitrite; Nitrites - blood; CVD; GTN; NO; eNOS; Nitric oxide; CAD; Nitrite; Endothelial function; FMD; Free radical; BA
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2006.04.006

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.