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Citations to this article

Hemolysis-associated endothelial dysfunction mediated by accelerated NO inactivation by decompartmentalized oxyhemoglobin
Peter C. Minneci, … , Mark T. Gladwin, Steven B. Solomon
Peter C. Minneci, … , Mark T. Gladwin, Steven B. Solomon
Published December 1, 2005
Citation Information: J Clin Invest. 2005;115(12):3409-3417. https://doi.org/10.1172/JCI25040.
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Research Article Vascular biology Article has an altmetric score of 9

Hemolysis-associated endothelial dysfunction mediated by accelerated NO inactivation by decompartmentalized oxyhemoglobin

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Abstract

During intravascular hemolysis in human disease, vasomotor tone and organ perfusion may be impaired by the increased reactivity of cell-free plasma hemoglobin (Hb) with NO. We experimentally produced acute intravascular hemolysis in a canine model in order to test the hypothesis that low levels of decompartmentalized or cell-free plasma Hb will severely reduce NO bioavailability and produce vasomotor instability. Importantly, in this model the total intravascular Hb level is unchanged; only the compartmentalization of Hb within the erythrocyte membrane is disrupted. Using a full-factorial design, we demonstrate that free water–induced intravascular hemolysis produces dose-dependent systemic vasoconstriction and impairs renal function. We find that these physiologic changes are secondary to the stoichiometric oxidation of endogenous NO by cell-free plasma oxyhemoglobin. In this model, 80 ppm of inhaled NO gas oxidized 85–90% of plasma oxyhemoglobin to methemoglobin, thereby inhibiting endogenous NO scavenging by cell-free Hb. As a result, the vasoconstriction caused by acute hemolysis was attenuated and the responsiveness to systemically infused NO donors was restored. These observations confirm that the acute toxicity of intravascular hemolysis occurs secondarily to the accelerated dioxygenation reaction of plasma oxyhemoglobin with endothelium-derived NO to form bioinactive nitrate. These biochemical and physiological studies demonstrate a major role for the intact erythrocyte in NO homeostasis and provide mechanistic support for the existence of a human syndrome of hemolysis-associated NO dysregulation, which may contribute to the vasculopathy of hereditary, acquired, and iatrogenic hemolytic states.

Authors

Peter C. Minneci, Katherine J. Deans, Huang Zhi, Peter S.T. Yuen, Robert A. Star, Steven M. Banks, Alan N. Schechter, Charles Natanson, Mark T. Gladwin, Steven B. Solomon

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 Total
Citations: 1 9 7 6 8 8 11 6 5 6 7 8 9 14 6 7 7 8 4 7 144
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Citations to this article in year 2010 (7)

Title and authors Publication Year
Pulmonary hypertension and NO in sickle cell
MT Gladwin, RJ Barst, OL Castro, VR Gordeuk, CA Hillery, GJ Kato, DB Kim-Shapiro, R Machado, CR Morris, MH Steinberg, EP Vichinsky
Blood 2010
Heme Degradation and Vascular Injury
JD Belcher, JD Beckman, G Balla, J Balla, G Vercellotti
Antioxidants & Redox Signaling 2010
Pulmonary hypertension in hemolytic anemias
S Wahl, E Vichinsky
F1000 medicine reports 2010
Reversal of hemoglobin-induced vasoconstriction with sustained release of nitric oxide
P Cabrales, G Han, P Nacharaju, AJ Friedman, JM Friedman
American journal of physiology. Heart and circulatory physiology 2010
INCREASED PULMONARY PRESSURES AND MYOCARDIAL WALL STRESS IN CHILDREN WITH SEVERE MALARIA*
JJ Janka, OA Koita, B Traoré, JM Traoré, F Mzayek, V Sachdev, X Wang, K Sanogo, L Sangaré, L Mendelsohn, H Masur, GJ Kato, MT Gladwin, DJ Krogstad
The Journal of Infectious Diseases 2010
Effects of a Single Sickling Event on the Mechanical Fragility of Sickle Cell Trait Erythrocytes
TD Presley, AS Perlegas, LE Bain, SK Ballas, JS Nichols, H Sabio, MT Gladwin, GJ Kato, DB Kim-Shapiro
Hemoglobin 2010
Association between Hemoglobin Level and Endothelial Function in Uncomplicated, Untreated Hypertensive Patients
R Maio, A Sciacqua, R Bruni, A Pascale, G Carullo, PE Scarpino, D Addesi, I Spinelli, GG Leone, F Perticone
Clinical journal of the American Society of Nephrology : CJASN 2010

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