Plasma Nitrosothiols Contribute to the Systemic Vasodilator Effects of Intravenously Applied NO: Experimental and Clinical Study on the Fate of NO in Human Blood

• Published in: Circulation research Vol. 91; no. 6; pp. 470 - 477
• Main Authors: Rassaf, Tienush, Kleinbongard, Petra, Preik, Michael, Dejam, André, Gharini, Putrika, Lauer, Thomas, Erckenbrecht, Julia, Duschin, Alexej, Schulz, Rainer, Heusch, Gerd, Feelisch, Martin, Kelm, Malte
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Heart Association, Inc 20.09.2002; Lippincott; Lippincott Williams & Wilkins Ovid Technologies
• Subjects: Adult; Biological and medical sciences; Female; Fundamental and applied biological sciences. Psychology; General aspects; Hemodynamics - drug effects; Humans; Infusions, Intravenous; Male; Nitrates - blood; Nitric Oxide - blood; Nitric Oxide - pharmacology; Nitrites - blood; Nitroso Compounds - blood; S-Nitrosoglutathione - blood; Time Factors; Vasodilation - drug effects; Vertebrates: cardiovascular system; Human; Nitroso compound; Intravenous administration; Biological transport; Metabolism; Biological activity; Vasodilation; Blood plasma; Vasomotricity; Nitric oxide; Blood vessel; Circulatory system; Hemodynamics
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.RES.0000035038.41739.CB

ABSTRACT—Higher doses of inhaled NO exert effects beyond the pulmonary circulation. How such extrapulmonary effects can be reconciled with the presumed short half-life of NO in the blood is unclear. Whereas erythrocytes have been suggested to participate in NO transport, the exact role of plasma in NO delivery in humans is not clear. Therefore, we investigated potential routes of NO decomposition and transport in human plasma. NO consumption in plasma was accompanied by a concentration-dependent increase in nitrite and S-nitrosothiols (RSNOs), with no apparent saturation limit up to 200 μmol/L. The presence of red blood cells reduced the formation of plasma RSNOs. Intravenous infusion of 30 μmol/min NO in healthy volunteers increased plasma levels of RSNOs and induced systemic hemodynamic effects at the level of both conduit and resistance vessels, as reflected by dilator responses in the brachial artery and forearm microvasculature. Intravenous application of S-nitrosoglutathione, a potential carrier of bioactive NO, mimicked the vascular effects of NO, whereas nitrite and nitrate were inactive. Changes in plasma nitrosothiols were correlated with vasodilator effects after intravenous application of S-nitrosoglutathione and NO. These findings demonstrate that in humans the pharmacological delivery of NO solutions results in the transport and delivery of NO as RSNOs along the vascular tree.