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 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Hagerstown, MD
American Heart Association, Inc
20.09.2002
Lippincott Lippincott Williams & Wilkins Ovid Technologies |
Subjects | |
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Abstract | 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. |
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AbstractList | 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 micro mol/L. The presence of red blood cells reduced the formation of plasma RSNOs. Intravenous infusion of 30 micro mol/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. 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. 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. |
Author | Feelisch, Martin Heusch, Gerd Dejam, André Gharini, Putrika Erckenbrecht, Julia Preik, Michael Duschin, Alexej Kelm, Malte Kleinbongard, Petra Lauer, Thomas Rassaf, Tienush Schulz, Rainer |
AuthorAffiliation | From the Department of Medicine (T.R., P.K., M.P., A.D., P.G., T.L., J.E., M.K.), Heinrich-Heine-University, Düsseldorf, Germany; the Department of Molecular and Cellular Physiology (T.R., M.F.), Louisiana State University, Shreveport, La; and the Institute of Pathophysiology (A.D., R.S., G.H.), University of Essen, Medical School, Essen, Germany. Both authors contributed equally to this study |
AuthorAffiliation_xml | – name: From the Department of Medicine (T.R., P.K., M.P., A.D., P.G., T.L., J.E., M.K.), Heinrich-Heine-University, Düsseldorf, Germany; the Department of Molecular and Cellular Physiology (T.R., M.F.), Louisiana State University, Shreveport, La; and the Institute of Pathophysiology (A.D., R.S., G.H.), University of Essen, Medical School, Essen, Germany. Both authors contributed equally to this study |
Author_xml | – sequence: 1 givenname: Tienush surname: Rassaf fullname: Rassaf, Tienush organization: From the Department of Medicine (T.R., P.K., M.P., A.D., P.G., T.L., J.E., M.K.), Heinrich-Heine-University, Düsseldorf, Germany; the Department of Molecular and Cellular Physiology (T.R., M.F.), Louisiana State University, Shreveport, La; and the Institute of Pathophysiology (A.D., R.S., G.H.), University of Essen, Medical School, Essen, Germany. Both authors contributed equally to this study – sequence: 2 givenname: Petra surname: Kleinbongard fullname: Kleinbongard, Petra – sequence: 3 givenname: Michael surname: Preik fullname: Preik, Michael – sequence: 4 givenname: André surname: Dejam fullname: Dejam, André – sequence: 5 givenname: Putrika surname: Gharini fullname: Gharini, Putrika – sequence: 6 givenname: Thomas surname: Lauer fullname: Lauer, Thomas – sequence: 7 givenname: Julia surname: Erckenbrecht fullname: Erckenbrecht, Julia – sequence: 8 givenname: Alexej surname: Duschin fullname: Duschin, Alexej – sequence: 9 givenname: Rainer surname: Schulz fullname: Schulz, Rainer – sequence: 10 givenname: Gerd surname: Heusch fullname: Heusch, Gerd – sequence: 11 givenname: Martin surname: Feelisch fullname: Feelisch, Martin – sequence: 12 givenname: Malte surname: Kelm fullname: Kelm, Malte |
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Snippet | ABSTRACT—Higher doses of inhaled NO exert effects beyond the pulmonary circulation. How such extrapulmonary effects can be reconciled with the presumed short... Higher doses of inhaled NO exert effects beyond the pulmonary circulation. How such extrapulmonary effects can be reconciled with the presumed short half-life... |
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SubjectTerms | 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 |
Title | Plasma Nitrosothiols Contribute to the Systemic Vasodilator Effects of Intravenously Applied NO: Experimental and Clinical Study on the Fate of NO in Human Blood |
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