Erythrocyte consumption of nitric oxide in presence and absence of plasma-based hemoglobin.

Experimental measurements have suggested a consumption rate of nitric oxide (NO) by red blood cells (RBCs) that is orders of magnitude smaller than that of an equivalent concentration of free hemoglobin in solution. This difference has been attributed to external diffusion limitations in the transport of NO from the plasma to the surface of the RBC or to resistance in the transport through the erythrocytic membrane. A detailed mathematical model is developed to quantify the resistance to NO transport around a single RBC and to predict the consumption rate in the presence and absence of extracellular hemoglobin. We provide a description for the NO consumption rate as a function of hematocrit, RBC radius, membrane permeability, and extracellular hemoglobin concentration. We predict a first-order rate constant for NO consumption in blood between 7.5 x 10(2) and 6.5 x 10(3) s(-1) at a hematocrit of 45% for membrane permeability values between 0.1 and 40 cm/s. Our results suggest that the difference in NO uptake by RBCs and free hemoglobin is smaller than previously reported and it is hematocrit dependent.

[1]  J. Liao,et al.  Modulation of nitric oxide bioavailability by erythrocytes , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[2]  S. Herold,et al.  Kinetic and mechanistic studies of the NO*-mediated oxidation of oxymyoglobin and oxyhemoglobin. , 2001, Biochemistry.

[3]  J. Liao,et al.  Erythrocyte consumption of nitric oxide: competition experiment and model analysis. , 2001, Nitric oxide : biology and chemistry.

[4]  J. Stamler,et al.  Export by red blood cells of nitric oxide bioactivity , 2001, Nature.

[5]  J Levin,et al.  Progress in the development of RBC substitutes , 2001, Transfusion.

[6]  R. Winslow.  Blood substitutes: refocusing an elusive goal , 2000, British journal of haematology.

[7]  R. Winslow.  Blood substitutes: refocusing an elusive goal. Review , 2000 .

[8]  R. Winslow.  αα–Crosslinked Hemoglobin: Was Failure Predicted by Preclinical Testing? , 2000, Vox Sanguinis.

[9]  R. Winslow.  αα‐Crosslinked Hemoglobin: Was Failure Predicted by Preclinical Testing? , 2000, Vox sanguinis.

[10]  J. Stamler,et al.  Functional Coupling of Oxygen Binding and Vasoactivity inS-Nitrosohemoglobin* , 2000, The Journal of Biological Chemistry.

[11]  J. Liao,et al.  Erythrocytes Possess an Intrinsic Barrier to Nitric Oxide Consumption* , 2000, The Journal of Biological Chemistry.

[12]  J. Stamler,et al.  The oxyhemoglobin reaction of nitric oxide. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[13]  A. Alayash.  Hemoglobin-based blood substitutes: oxygen carriers, pressor agents, or oxidants? , 1999, Nature Biotechnology.

[14]  I. Megson,et al.  Diffusion of nitric oxide and scavenging by blood in the vasculature. , 1998, Biochimica et biophysica acta.

[15]  Xiaoping Liu,et al.  Diffusion-limited Reaction of Free Nitric Oxide with Erythrocytes* , 1998, The Journal of Biological Chemistry.

[16]  James C. Liao,et al.  Estimation of nitric oxide production and reactionrates in tissue by use of a mathematical model. , 1998, American journal of physiology. Heart and circulatory physiology.

[17]  J. Liao,et al.  Effective diffusion distance of nitric oxide in the microcirculation. , 1998, American journal of physiology. Heart and circulatory physiology.

[18]  Xiaoping Liu,et al.  Accelerated reaction of nitric oxide with O2 within the hydrophobic interior of biological membranes. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[19]  J S Beckman,et al.  Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. , 1996, The American journal of physiology.

[20]  J. Olson,et al.  Mechanism of NO-induced oxidation of myoglobin and hemoglobin. , 1996, Biochemistry.

[21]  J. S. Hyde,et al.  Permeability of nitric oxide through lipid bilayer membranes. , 1996, Free radical research.

[22]  J. Ulatowski,et al.  Regional blood flow alterations after bovine fumaryl beta beta-crosslinked hemoglobin transfusion and nitric oxide synthase inhibition. , 1996, Critical care medicine.

[23]  E. Lissi,et al.  Nitric oxide diffusion in membranes determined by fluorescence quenching. , 1996, Archives of biochemistry and biophysics.

[24]  S. Goldstein,et al.  The reaction of NO. with O2.- and HO2.: a pulse radiolysis study. , 1995, Free radical biology & medicine.

[25]  J. Wood,et al.  Models of the diffusional spread of nitric oxide: Implications for neural nitric oxide signalling and its pharmacological properties , 1994, Neuropharmacology.

[26]  J. Lancaster,et al.  Simulation of the diffusion and reaction of endogenously produced nitric oxide. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[27]  P Tomboulian,et al.  Diffusion of nitric oxide in the aorta wall monitored in situ by porphyrinic microsensors. , 1993, Biochemical and biophysical research communications.

[28]  L. Ignarro,et al.  Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[29]  S. Moncada,et al.  Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor , 1987, Nature.

[30]  M. Sato.  [Mechanical properties of living tissues]. , 1986, Iyo denshi to seitai kogaku. Japanese journal of medical electronics and biological engineering.

[31]  V. H. Huxley,et al.  Effect of diffusion boundary layers on the initial uptake of O2 by red cells. Theory versus experiment. , 1983, Microvascular research.

[32]  V. Huxley,et al.  The effect of the red cell membrane and a diffusion boundary layer on the rate of oxygen uptake by human erythrocytes , 1981, The Journal of physiology.

[33]  R. Furchgott,et al.  The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine , 1980, Nature.

[34]  F. Kreuzer,et al.  Diffusion coefficients of oxygen and hemoglobin as obtained simultaneously from photometric determination of the oxygenation of layers of hemoglobin solutions , 1980, Pflügers Archiv.

[35]  J. Olson,et al.  The rate of oxygen uptake by human red blood cells. , 1979, The Journal of biological chemistry.

[36]  Q. Gibson,et al.  Conformation, co-operativity and ligand binding in human hemoglobin. , 1975, Journal of molecular biology.

[37]  J. H. Comroe,et al.  THE RATE OF UPTAKE OF CARBON MONOXIDE AND OF NITRIC OXIDE BY NORMAL HUMAN ERYTHROCYTES AND EXPERIMENTALLY PRODUCED SPHEROCYTES , 1958, The Journal of general physiology.

[38]  D. Buerk,et al.  Can we model nitric oxide biotransport? A survey of mathematical models for a simple diatomic molecule with surprisingly complex biological activities. , 2001, Annual review of biomedical engineering.

[39]  J. Ulatowski,et al.  Sustained endothelial dependent dilation in pial arterioles after crosslinked hemoglobin transfusion. , 1997, Artificial cells, blood substitutes, and immobilization biotechnology.

[40]  J. Ulatowski,et al.  Role of nitric oxide scavenging in peripheral vasoconstrictor response to beta beta cross-linked hemoglobin. , 1995, Artificial cells, blood substitutes, and immobilization biotechnology.

[41]  J. Ulatowski,et al.  Role of Nitric Oxide Scavenging in Peripheral Vasoconstrictor Response to ββ Cross-Linked Hemoglobin , 1995 .

[42]  T. K. Goldstick,et al.  Diffusion of oxygen in plasma and blood. , 1976, Advances in experimental medicine and biology.

[43]  Philip L. Altman,et al.  Respiration and Circulation , 1971 .