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

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...

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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
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Summary:	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.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	0009-7330 1524-4571
DOI:	10.1161/01.RES.0000035038.41739.CB