Serum nitrite sensitively reflects endothelial NO formation in human forearm vasculature: evidence for biochemical assessment of the endothelial L-arginine-NO pathway.

摘要: Objective: A reduced bioactivity of endothelial nitric oxide (NO) has been implicated in the pathogenesis atherosclerosis. In humans, l-arginine–NO pathway indirectly assessed via flow response to endothelium-dependent vasodilators locally administered into coronary, pulmonary or forearm circulation. However, biochemical quantification NO formation these organ circulations hampered so far because rapid metabolism NO. Therefore, we aimed work out a reliable index assess human Methods: 33 healthy volunteers, blood (FBF) was measured by standard techniques venous occlusion plethysmography at rest, after local application vasodilator acetylcholine (ACH), endothelium-independent papaverine (PAP), stereospecific inhibitor synthase (eNOS) L-NMMA, and l-arginine (ARG), natural substrate eNOS. parallel, nitrite nitrate concentrations samples taken from antecubital vein were HPLC using anion-exchange chromatography combination with electrochemical ultraviolet detection following specific sample preparation method. Results: ACH dose-dependently increased resting FBF (from 3.0±0.3 10.4±0.9 ml/min per 100 ml tissue) serum concentration 402±59 977±82 nmol/l, both p <0.05, n =12). significant correlation observed between changes ( r =0.61, <0.0001). L-NMMA vasodilation 30% this paralleled reduction highest dose =9, <0.001). PAP more than fourfold, but did not affect =11), whereas ARG significantly nitrite. Basal amounted 25±4 μmol/l remained constant during ACH, L-NMMA. Conclusions: The sensitively reflects This measure may help characterize disease states associated dysfunction further elucidate its pathophysiological significance for development atherosclerosis humans.