Endothelial Nitric Oxide Production and Transport in Flow Chambers: The Importance of Convection

A computational model of Nitric Oxide (NO) production and transport within a parallel-plate flow chamber coated with endothelial cells is presented. The relationship between NO concentration and Wall Shear Stress (WSS) at the endothelium is investigated in detail. An increase in WSS is associated with two phenomena: enhanced NO production by the endothelial cells, and an increase in the velocity at which NO is convected out of the chamber. These two phenomena have opposite effects on endothelial NO concentration. In physiologically realistic cases, the balance between them is found to vary as WSS is raised, resulting in a complex non-monotonic dependence of endothelial NO concentration on WSS. Also, it is found that a NO concentration boundary layer develops within the chamber, leading to substantial spatial variations in NO concentration along the length of the device. Finally, the implications of a negative feedback mechanism (that affects NO production) are presented. The results emphasize the role of convection on NO transport within flow chambers, which has been overlooked or misinterpreted in most previous theoretical studies. It is hoped that the conclusions of this study can be used to aid accurate interpretation of related experimental data.

[1]  R. Schroter,et al.  Arterial Wall Shear and Distribution of Early Atheroma in Man , 1969, Nature.

[2]  A. Bejan.  Convection Heat Transfer , 1984 .

[3]  R. Probstein.  Physicochemical Hydrodynamics: An Introduction , 1989 .

[4]  D. Wink,et al.  Reactions of the bioregulatory agent nitric oxide in oxygenated aqueous media: determination of the kinetics for oxidation and nitrosation by intermediates generated in the NO/O2 reaction. , 1993, Chemical Research in Toxicology.

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

[6]  W. Deen,et al.  Kinetics of the reaction of nitric oxide with oxygen in aqueous solutions. , 1994, Chemical research in toxicology.

[7]  M. Kuchan,et al.  Role of calcium and calmodulin in flow-induced nitric oxide production in endothelial cells. , 1994, The American journal of physiology.

[8]  V. Kharitonov,et al.  Kinetics of nitric oxide autoxidation in aqueous solution. , 1994, The Journal of biological chemistry.

[9]  G. Truskey,et al.  Shear stress induces ATP-independent transient nitric oxide release from vascular endothelial cells, measured directly with a porphyrinic microsensor. , 1995, Circulation research.

[10]  J A Frangos,et al.  Steady shear and step changes in shear stimulate endothelium via independent mechanisms--superposition of transient and sustained nitric oxide production. , 1996, Biochemical and biophysical research communications.

[11]  E. Camporesi,et al.  Half-life of nitric oxide in aqueous solutions with and without haemoglobin , 1996, Physiological measurement.

[12]  R M Nerem,et al.  A mathematical model of the cytosolic-free calcium response in endothelial cells to fluid shear stress. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[13]  T. Irimura,et al.  Direct evidence of nitric oxide production from bovine aortic endothelial cells using new fluorescence indicators: diaminofluoresceins , 1998, FEBS letters.

[14]  J. Liao,et al.  Effective diffusion distance of nitric oxide in the microcirculation. , 1998, The American journal of physiology.

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

[16]  M. Kelm.  Nitric oxide metabolism and breakdown. , 1999, Biochimica et biophysica acta.

[17]  S. Alper,et al.  Hemodynamic shear stress and its role in atherosclerosis. , 1999, JAMA.

[18]  T. Nagano.  Practical methods for detection of nitric oxide. , 1999, Luminescence : the journal of biological and chemical luminescence.

[19]  J. Loscalzo.  Endothelium, Nitric Oxide, and Atherosclerosis: From Basic Mechanisms to Clinical Implications , 2000 .

[20]  D. Kass,et al.  Determinants of shear stress-stimulated endothelial nitric oxide production assessed in real-time by 4,5-diaminofluorescein fluorescence. , 2001, Biochemical and biophysical research communications.

[21]  Kayne M. Smith,et al.  Advective transport of nitric oxide in a mathematical model of the afferent arteriole. , 2003, American journal of physiology. Renal physiology.

[22]  Aleksander S Popel,et al.  Wall shear stress differentially affects NO level in arterioles for volume expanders and Hb-based O2 carriers. , 2003, Microvascular research.

[23]  C. R. Ethier,et al.  Computational Modeling of Mass Transfer and Links to Atherosclerosis , 2002, Annals of Biomedical Engineering.

[24]  Tim David,et al.  Wall Shear Stress Modulation of ATP/ADP Concentration at the Endothelium , 2003, Annals of Biomedical Engineering.

[25]  G. Karniadakis,et al.  Spectral/hp Element Methods for Computational Fluid Dynamics , 2005 .

[26]  Rob Krams,et al.  Shear stress affects the intracellular distribution of eNOS: direct demonstration by a novel in vivo technique. , 2005, Blood.

[27]  D. Harrison,et al.  A negative feedback mechanism involving nitric oxide and nuclear factor kappa-B modulates endothelial nitric oxide synthase transcription. , 2005, Journal of molecular and cellular cardiology.

[28]  M. Gladwin,et al.  Nitric Oxide Scavenging by Red Blood Cells as a Function of Hematocrit and Oxygenation* , 2005, Journal of Biological Chemistry.

[29]  Aleksander S Popel,et al.  Theoretical analysis of biochemical pathways of nitric oxide release from vascular endothelial cells. , 2006, Free radical biology & medicine.

[30]  J. Ando,et al.  Impaired flow-dependent control of vascular tone and remodeling in P2X4-deficient mice , 2006, Nature Medicine.

[31]  J. Frangos,et al.  The shear stress of it all: the cell membrane and mechanochemical transduction , 2007, Philosophical Transactions of the Royal Society B: Biological Sciences.

[32]  M. Plank,et al.  The role of endothelial calcium and nitric oxide in the localisation of atherosclerosis. , 2007, Mathematical biosciences.

[33]  P. Serruys,et al.  Rapamycin modulates the eNOS vs. shear stress relationship. , 2008, Cardiovascular research.

[34]  Aleksander S Popel,et al.  Nitric oxide in the vasculature: where does it come from and where does it go? A quantitative perspective. , 2008, Antioxidants & redox signaling.

[35]  D. Jaron,et al.  A Computational Model of Nitric Oxide Production and Transport in a Parallel Plate Flow Chamber , 2009, Annals of Biomedical Engineering.