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This Article Full Text Full Text (PDF) All Versions of this Article: 287/6/H2561    most recent 00310.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Deem, S. Articles by Gladwin, M. T. Search for Related Content PubMed PubMed Citation Articles by Deem, S. Articles by Gladwin, M. T.

Pulmonary vascular effects of red blood cells containing S-nitrosated hemoglobin

¹Departments of Anesthesiology and Medicine, Pulmonary and Critical Care, University of Washington Veterans Affairs Puget Sound Health Care Center, Seattle, Washington 98104-2499; ²Department of Anesthesiology, College of Medicine, University of Ulsan, Asan Medical Center, Kangnung 682-714, Korea; ³Department of Anesthesiology, Myongji Hospital, Kwandong University, Kwandong 412-270, Korea; and ⁴Critical Care Medicine Department, Clinical Center, and Laboratory of Chemical Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892

Submitted 29 March 2004 ; accepted in final form 26 July 2004

The role of S-nitrosated hemoglobin (SNO-Hb) in the regulation of blood flow is a central and controversial question in cardiopulmonary physiology. In the present study, we investigate whether intact human red blood cells (RBCs) synthesized to contain high SNO-Hb levels are able to export nitric oxide bioactivity and vasodilate the pulmonary circulation, and whether SNO-Hb dependent vasodilation occurs secondary to an intrinsic oxygen-linked, allosteric function of Hb. RBCs containing supraphysiological concentrations (100–1,000x normal) of SNO-Hb (SNO-RBCs) were synthesized and added to isolated, perfused rat lungs during anoxic or normoxic ventilation, and during normoxic ventilation with pulmonary hypertension induced by the thromboxane mimetic U-46619. SNO-RBCs produced dose-dependent pulmonary vasodilation compared with control RBCs during conditions of both normoxic (U-46619) and hypoxic pulmonary vasoconstriction. These effects were associated with a simultaneous, rapid, and temperature-dependent loss of SNO from Hb. Both vasodilatory effects and the rate of SNO-Hb degradation were independent of oxygen tension and Hb oxygen saturation. Furthermore, these effects were not affected by inhibition of the RBC membrane band 3 protein (anion exchanger-1), a putative membrane facilitator of NO export from RBCs. Whereas these data support observations by multiple groups that synthesized SNO-Hb can vasodilate, this effect is not under intrinsic oxygen-dependent allosteric control, nor likely to be relevant in the pulmonary circulation at normal physiological concentrations.

nitric oxide; hypoxic pulmonary vasoconstriction; erythrocytes

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