{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T13:52:36Z","timestamp":1791208356442,"version":"4.1.0"},"reference-count":41,"publisher":"National Academy of Sciences","issue":"22","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,10,23]]},"abstract":"<jats:p>\n                    The plasma level of NO\n                    <jats:sub>x<\/jats:sub>\n                    , i.e., the sum of NO\n                    <jats:sub>2<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    and NO\n                    <jats:sub>3<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    , is frequently used to assess NO bioavailability\n                    <jats:italic>in vivo<\/jats:italic>\n                    . However, little is known about the kinetics of NO conversion to these metabolites under physiological conditions. Moreover, plasma nitrite recently has been proposed to represent a delivery source for intravascular NO. We therefore sought to investigate in humans whether changes in NO\n                    <jats:sub>x<\/jats:sub>\n                    concentration are a reliable marker for endothelial NO production and whether physiological concentrations of nitrite are vasoactive. NO\n                    <jats:sub>2<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    and NO\n                    <jats:sub>3<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    concentrations were measured in blood sampled from the antecubital vein and brachial artery of 24 healthy volunteers. No significant arterial-venous gradient was observed for either NO\n                    <jats:sub>2<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    or NO\n                    <jats:sub>3<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    . Endothelial NO synthase (eNOS) stimulation with acetylcholine (1\u201310 \u03bcg\/min) dose-dependently augmented venous NO\n                    <jats:sub>2<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    levels by maximally 71%. This effect was paralleled by an almost 4-fold increase in forearm blood flow (FBF), whereas an equieffective dose of papaverine produced no change in venous NO\n                    <jats:sub>2<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    . Intraarterial infusion of NO\n                    <jats:sub>2<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    had no effect on FBF. NOS inhibition (N\n                    <jats:sup>G<\/jats:sup>\n                    -monomethyl-\n                    <jats:sc>l<\/jats:sc>\n                    -arginine; 4\u201312 \u03bcmol\/min) dose-dependently reduced basal NO\n                    <jats:sub>2<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    and FBF and blunted acetylcholine-induced vasodilation and NO release by more than 80% and 90%, respectively. In contrast, venous NO\n                    <jats:sub>3<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    and total NO\n                    <jats:sub>x<\/jats:sub>\n                    remained unchanged as did systemic arterial NO\n                    <jats:sub>2<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    and NO\n                    <jats:sub>3<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    levels during all these interventions. FBF and NO release showed a positive association (\n                    <jats:italic>r<\/jats:italic>\n                    = 0.85;\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.001). These results contradict the current paradigm that plasma NO\n                    <jats:sub>3<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    and\/or total NO\n                    <jats:sub>x<\/jats:sub>\n                    are generally useful markers of endogenous NO production and demonstrate that only NO\n                    <jats:sub>2<\/jats:sub>\n                    <jats:sup>\u2212<\/jats:sup>\n                    reflects acute changes in regional eNOS activity. Our results further demonstrate that physiological levels of nitrite are vasodilator-inactive.\n                  <\/jats:p>","DOI":"10.1073\/pnas.221381098","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:37:36Z","timestamp":1027679856000},"page":"12814-12819","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":498,"title":["Plasma nitrite rather than nitrate reflects regional endothelial nitric oxide synthase activity but lacks intrinsic vasodilator action"],"prefix":"10.1073","volume":"98","author":[{"given":"Thomas","family":"Lauer","sequence":"first","affiliation":[{"name":"Klinik f\u00fcr Kardiologie, Pneumologie, und Angiologie, Heinrich-Heine-Universit\u00e4t Moorenstrasse 5, D-40225 D\u00fcsseldorf, Germany; Institut f\u00fcr Physiologie, Medizinische Fakult\u00e4t Carl Gustav Carus, Technische Universit\u00e4t Dresden, D-01307 Dresden, Germany; and Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA 71130"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Preik","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Kardiologie, Pneumologie, und Angiologie, Heinrich-Heine-Universit\u00e4t Moorenstrasse 5, D-40225 D\u00fcsseldorf, Germany; Institut f\u00fcr Physiologie, Medizinische Fakult\u00e4t Carl Gustav Carus, Technische Universit\u00e4t Dresden, D-01307 Dresden, Germany; and Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA 71130"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tienush","family":"Rassaf","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Kardiologie, Pneumologie, und Angiologie, Heinrich-Heine-Universit\u00e4t Moorenstrasse 5, D-40225 D\u00fcsseldorf, Germany; Institut f\u00fcr Physiologie, Medizinische Fakult\u00e4t Carl Gustav Carus, Technische Universit\u00e4t Dresden, D-01307 Dresden, Germany; and Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA 71130"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bodo E.","family":"Strauer","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Kardiologie, Pneumologie, und Angiologie, Heinrich-Heine-Universit\u00e4t Moorenstrasse 5, D-40225 D\u00fcsseldorf, Germany; Institut f\u00fcr Physiologie, Medizinische Fakult\u00e4t Carl Gustav Carus, Technische Universit\u00e4t Dresden, D-01307 Dresden, Germany; and Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA 71130"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Deussen","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Kardiologie, Pneumologie, und Angiologie, Heinrich-Heine-Universit\u00e4t Moorenstrasse 5, D-40225 D\u00fcsseldorf, Germany; Institut f\u00fcr Physiologie, Medizinische Fakult\u00e4t Carl Gustav Carus, Technische Universit\u00e4t Dresden, D-01307 Dresden, Germany; and Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA 71130"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Feelisch","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Kardiologie, Pneumologie, und Angiologie, Heinrich-Heine-Universit\u00e4t Moorenstrasse 5, D-40225 D\u00fcsseldorf, Germany; Institut f\u00fcr Physiologie, Medizinische Fakult\u00e4t Carl Gustav Carus, Technische Universit\u00e4t Dresden, D-01307 Dresden, Germany; and Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA 71130"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malte","family":"Kelm","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr 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