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Nitric Oxide in the Vascular System: Meet a Challenge

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Bioengineering in Cell and Tissue Research

Abstract

After a small introduction in the topic and relative young history of nitric oxide (NO) we would like to illustrate a few aspects of the wide field in NO research in biomedicine. The theoretical background of NO metabolism is spiked with numerous examples of methodologies from bioassays to biochemistry. Furthermore, first steps in the realization of new concepts in NO research in microcirculation are developed.

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References

  1. Pryor WA (1998) Nitric oxide. General introduction. Free Radic Biol Med 25:383

    Article  Google Scholar 

  2. Kuo PC, Schroeder RA (1995) The emerging multifaceted roles of nitric oxide. Ann Surg 221:220–235

    Article  Google Scholar 

  3. Moncada S, Higgs A (1993) The L-arginine-nitric oxide pathway. N Engl J Med 329:2002–2012

    Article  Google Scholar 

  4. Alderton WK, Cooper CE, Knowles RG (2001) Nitric oxide synthases: structure, function and inhibition. Biochem J 357:593–615

    Article  Google Scholar 

  5. Förstermann U, Kleinert H (1995) Nitric oxide synthase: expression and expressional control of the three isoforms. Naunyn Schmiedebergs Arch Pharmacol 352:351–364

    Article  Google Scholar 

  6. Ignarro LJ, Kadowitz PJ (1985) Pharmacological and physiological role of cGMP in vascular smooth muscle relaxation. Annu Rev Pharmacol Toxicol 25:171–191

    Article  Google Scholar 

  7. Moncada S (1997) Nitric oxide in the vasculature: physiology and pathophysiology. Ann N Y Acad Sci 811:60–69

    Article  Google Scholar 

  8. Arnold WP, Mittal CK, Katsuki S, Murad F (1977) Nitric oxide activates guanylate cyclase and increases guanosine 3’:5’-cyclic monophosphate levels in various tissue preparations. Proc Natl Acad Sci USA 74:3203–3207

    Article  Google Scholar 

  9. Furchgott RF, Zawadzki JV (1980) The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288:373–376

    Article  Google Scholar 

  10. Ignarro LJ, Buga GM, Wood KS, Byrns RE, Chaudhuri G (1987) Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci USA 84:9265–9269

    Article  Google Scholar 

  11. Palmer RMJ, Ferrige AG, Moncada S (1987) Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327:524–526

    Article  Google Scholar 

  12. Ignarro LJ, Cirino G, Casini A, Napoli C (1999) Nitric oxide as a signaling molecule in the vascular system: An overview. J Cardiovasc Pharmacol 34:879–886

    Article  Google Scholar 

  13. Radomski MW, Palmer RM, Moncada S (1990) An L-arginine/nitric oxide pathway present in human platelets regulates aggregation. Proc Natl Acad Sci USA 87:5193–5197

    Article  Google Scholar 

  14. Radomski MW, Palmer RMJ, Moncada S (1987) Endogenous nitric oxide inhibits human platelet adhesion to vascular endothelium. Lancet 7:1057–1058

    Article  Google Scholar 

  15. Starzyk D, Korbut R, Gryglewski RJ (1999) Effects of nitric oxide and prostacyclin on deformability and aggregability of red blood cells of rats ex vivo and in vitro. J Physiol Pharmacol 50:629–637

    Google Scholar 

  16. Arnal J-F, Dinh-Xuan A-T, Pueyo M, Darblade B, Rami J (1999) Endothelium-derived nitric oxide and vascular physiology and pathology. Cell Mol Life Sci 55:1078–1087

    Article  Google Scholar 

  17. Kawashima S, Yokoyama M (2004) Dysfunction of endothelial nitric oxide synthase and atherosclerosis. Arterioscler Thromb Vasc Biol 24:998–1005

    Article  Google Scholar 

  18. Vallance P, Chan N (2001) Endothelial function and nitric oxide: clinical relevance. Heart 85:342–350

    Article  Google Scholar 

  19. Rapoport RM, Murad F (1983) Agonist-induced endothelium-dependent relaxation in rat thoracic aorta may be mediated through cGMP. Circ Res 52:352–357

    Google Scholar 

  20. van de Voorde J, Leusen I (1986) Endothelium-dependent and independent relaxation of aortic rings from hypertensive rats. Am J Physiol Heart Circ Physiol 250:H711–H717

    Google Scholar 

  21. Horio Y, Yasue H, Rokutanda M et al. (1986) Effects of intracoronary injection of acetylcholine on coronary arterial diameter. Am J Cardiol 57:984–989

    Article  Google Scholar 

  22. Takase B, Hamabe A, Satomura K et al. (2006) Comparable prognostic value of vasodilator response to acetylcholine in brachial and coronary arteries for predicting long-term cardiovascular events in suspected coronary artery disease. Circulation 70:49–56

    Article  Google Scholar 

  23. Coretti MC, Anderson TJ, Benjamin EJ et al. (2002) Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery. J Am Coll Cardiol 39:257–265

    Article  Google Scholar 

  24. Joannides R, Haefeli WE, Linder L et al. (1995) Nitric oxide is responsible for flow-dependent dilatation of human peripheral conduit arteries in vivo. Circulation 91:1314–1319

    Google Scholar 

  25. Celermajer DS, Sorensen KE, Bull C, Robinson J, Deanfield JE (1994) Endothelium-dependent dilation in the systemic arteries of asymptomatic subjects relates to coronary risk factors and their interaction. J Am Coll Cardiol 24:1468–1474

    Article  Google Scholar 

  26. Kelm M (2002) Flow-mediated dilatation in human circulation: diagnostic and therapeutic aspects. Am J Physiol Heart Circ Physiol 282:H1–H5

    Google Scholar 

  27. Lorenz MW, Markus HS, Bots ML, Rosvall M, Sitzer M (2007) Prediction of clinical cardiovascular events with carotid intima-media thickness: a systematic review and meta-analysis. Circulation 115:459–467

    Article  Google Scholar 

  28. Kelm M, Strauer BE (2002) Microvascular dysfunction and myocardial ischaemia in hypertensive patients. Excerpta Medica 12:4–7

    Google Scholar 

  29. Tarpey MM, Fridovich I (2001) Methods of detection of vascular reactive species Nitric Oxide, Superoxide, Hydrogen Peroxide, and Peroxynitrite. Circ Res 89:224–236

    Article  Google Scholar 

  30. Kelm M, Dahmann R, Wink D, Feelisch M (1997) The nitric oxide-superoxide assay: insights into the biological chemistry of the NO/O2-interaction. J Biol Chem 272:9922–9932

    Article  Google Scholar 

  31. Kojima H, Nakatsubo N, Kikuchi K et al. (1998) Detection and imaging of nitric oxide with novel fluorescent indicators: diaminofluoresceins. Anal Chem 70:2446–2453

    Article  Google Scholar 

  32. Porasuphatana S, Weaver J, Budzichowski TA, Tsai P, Rosen GM (2001) Differential effect of buffer on the spin trapping of nitric oxide by iron chelates. Anal Biochem 298:50–56

    Article  Google Scholar 

  33. Heger J, Gödecke A, Flögel U et al. (2002) Cardiac-specific overexpression of inducible nitric oxide synthase does not result in severe cardiac dysfunction. Circ Res 90:93–99

    Article  Google Scholar 

  34. Kelm M (1999) Nitric oxide metabolism and breakdown. Biochim Biophys Acta 1411:273–289

    Article  Google Scholar 

  35. Stamler JS, Jaraki O, Osborne J et al. (1992) Nitric oxide circulates in mammalian plasma primarily as S-nitroso adduct of serum albumin. Proc Natl Acad Sci USA 89:7674–7677

    Article  Google Scholar 

  36. Ignarro LJ, Lippton H, Edwards JC et al. (1981) Mechanism of vascular smooth muscle relaxation by organic nitrates, nitrites, nitroprusside and nitric oxide: evidence for the involvement of S-nitrosothiols as active intermediates. J Pharmacol Exp Ther 218:739–749

    Google Scholar 

  37. Rassaf T, Preik M, Kleinbongard P et al. (2002) Evidence for in vivo transport of bioactive nitric oxide in human plasma. J Clin Invest 109:1241–1248

    Google Scholar 

  38. Rassaf T, Kleinbongard P, Preik M et al. (2002) Plasma nitrosothiols contribute to the systemic vasodilator effects of intravenously applied NO: experimental and clinical study on the fate of NO in human blood. Circ Res 91:470–477

    Article  Google Scholar 

  39. Grau M, Hendgen-Cotta U, Brouzos P et al. (2007) Recent methodological advances in the analysis of nitrite in the human circulation: Nitrite as a biochemical parameter of the L-arginine/NO pathway. Journal of Chromatography B 851:106–123

    Article  Google Scholar 

  40. Griess JP (1879) Bemerkungen zu der Abhandlung der HH. Wesely und Benedikt “Über einige Azoverbindungen”. Ber Deutsch Chem Ges 12:426–428

    Article  Google Scholar 

  41. Kleinbongard P, Rassaf T, Dejam A, Kerber S, Kelm M (2002) Griess method for nitrite measurement of aqueous and protein-containing sample. Methods Enzymol 359:158–168

    Article  Google Scholar 

  42. Preik-Steinhoff H, Kelm M (1996) Determination of nitrite in human blood by combination of a specific sample preparation with high performance anion-exchange chromatography and electrochemical determination. J Chromatogr B Biomed Appl 685:348–352

    Article  Google Scholar 

  43. Kleinbongard P, Dejam A, Lauer T et al. (2003) Plasma nitrite reflects constitutive nitric oxide synthase activity in mammals. Free Radic Biol Med 35:790–796

    Article  Google Scholar 

  44. Kleinbongard P, Dejam A, Lauer T et al. (2006) Plasma nitrite concentrations reflect the degree of endothelial dysfunction in humans. Free Radic Biol Med 40:295–302

    Article  Google Scholar 

  45. Doyle MP, Hoekstra JW (1981) Oxidation of nitrogen oxides by bound dioxygen in hemoproteins. J Inorg Biochem 14:351–358

    Article  Google Scholar 

  46. McMahon T, Moon RE, Luschinger BP et al. (2002) Nitric oxide in the human respiratory cycle. Nat Med 8:711–717

    Google Scholar 

  47. Joshi MS, Ferguson TB Jr, Han TH et al. (2002) Nitric oxide is consumed, rather than conserved, by reaction with oxyhemoglobin under physiological conditions. Proc Natl Acad Sci USA 99:10341–10346

    Article  Google Scholar 

  48. Lancaster JR Jr (1997) A tutorial on the diffusibility and reactivity of free nitric oxide. Nitric Oxide 1:18–30

    Article  Google Scholar 

  49. Liao JC, Hein TW, Vaughn MW, Huang K-T, Kuo L (1999) Intravascular flow decreases erythrocyte consumption of nitric oxide. Proc Natl Acad Sci USA 96:8757–8761

    Article  Google Scholar 

  50. Liu X, Miller MJ, Joshi MS et al. (1998) Diffusion-limited reaction of free nitric oxide with erythrocytes. J Biol Chem 273:18709–18713

    Article  Google Scholar 

  51. Vaughn MW, Huang KT, Kuo L, Liao JC (2000) Erythrocytes possess an intrinsic barrier to nitric oxide consumption. J Biol Chem 275:2342–2348

    Article  Google Scholar 

  52. Wennmalm A, Benthin G, Edlund A et al. (1993) Metabolism and excretion of nitric oxide in humans. An experimental and clinical study. Circ Res 73:1121–1127

    Google Scholar 

  53. Stamler JS, Jia L, Eu JP et al. (1997) Blood flow regulation by S-nitrosohemoglobin in the physiological oxygen gradient. Science 276:2034–2037

    Article  Google Scholar 

  54. McMahon TJ, Stone AE, Bonaventura J, Singel DJ, Stamler JS (2000) Functional coupling of oxygen binding and vasoactivity in S-nitrosohemoglobin. J Biol Chem 275:16738–16745

    Article  Google Scholar 

  55. Gladwin MT (2005) Nitrite as an intrinsic signaling molecule. Nature Chemical Biology 1:245–246

    Article  Google Scholar 

  56. Dejam A, Hunter CJ, Schechter AN, Gladwin MT (2004) Emerging role of nitrite in human biology. Blood Cells Mol Dis 32:423–429

    Article  Google Scholar 

  57. Dejam A, Hunter CJ, Pelletier MM et al. (2005) Erythrocytes are the Major Intravascular Storage Sites of Nitrite in Human Blood. Blood 106:734–739

    Article  Google Scholar 

  58. Hickey M, Granger D (2001) Inducible nitric oxide synthase (iNOS) and regulation of leucocyte/endothelial cell interactions: studies in iNOS-deficient mice. Acta Physiol Scand 173:119–126

    Article  Google Scholar 

  59. Freedman JE, Sauter R, Battinelli EM et al. (1999) Deficient platelet-derived nitric oxide and enhanced hemostasis in mice lacking the NOSIII gene. Circ Res 84:1416–1421

    Google Scholar 

  60. Metha JL, Metha P, Li D (2000) Nitric oxide synthase in adult red blood cells: vestige of an earlier age or a biologically active enzyme? J Lab Clin Med 135:430–431

    Article  Google Scholar 

  61. Kleinbongard P, Schulz R, Rassaf T et al. (2006) Red blood cells express a functional endothelial nitric oxide synthase. Blood 107:2943–2951

    Article  Google Scholar 

  62. Teichert A-M, Miller TL, Tai SC et al. (2000) In vivo expression profile of an endothelial nitric oxide synthase promoter-reporter transgene. Am J Physiol Heart Circ Physiol 278:H1352–H1361

    Google Scholar 

  63. Reid HL, Barnes AJ, Lock PJ, Dormandy JA, Dormandy TL (1976) Technical methods. A simple method for measuring erythrocyte deformability. J Clin Path 29:855–858

    Article  Google Scholar 

  64. Dobbe JG, Streekstra GJ, Hardeman MR, Ince C, Grimbergen CA (2002) Measurement of the distribution of red blood cell deformability using an automated rheoscope. Cytometry 50:313–325

    Article  Google Scholar 

  65. Maggakis-Kelemen C, Biselli M, Artmann GM (2002) Determination of the elastic shear modulus of cultured human red blood cells. Biomed Tech (Berl) 47:106–109

    Article  Google Scholar 

  66. Artmann GM, Paul Sung K-L, Horn T et al. (1997) Micropipette Aspiration of Human Erythrocytes Induces Echinocytes via Membrane Phospholipid Translocation. Biophys J 72:1434–1441

    Article  Google Scholar 

  67. Ruschitzka FT, Wenger RH, Stallmach T et al. (2000) Nitric oxide prevents cardiovascular disease and determines survival in polyglobulic mice overexpressing erythropoietin. Proc Natl Acad Sci USA 97:11609–11613

    Article  Google Scholar 

  68. Tsuda K, Kimura K, Nishio I, Masuyama Y (2000) Nitric oxide improves membrane fluidity of erythrocytes in essential hypertension: an electron paramagnetic resonance investigation. Biochem Biophys Res Commun 275:946–954

    Article  Google Scholar 

  69. Bor-Kucukatay M, Wenby RB, Meiselman HJ, Baskurt OK (2003) Effects of nitric oxide on red blood cell deformability. Am J Physiol Heart Circ Physiol 284:H1577–H1584

    Google Scholar 

  70. Reiter CD, Wang X, Tanus-Santos JE et al. (2002) Cell – free hemoglobin limits nitric oxide bioavailability in sickle – cell disease. Nat Med 8:1383–1389

    Article  Google Scholar 

  71. Weiner DL, Hibberd PL, Betit P et al. (2003) Preliminary assessment of inhaled nitric oxide for acute vaso-occlusive crisis in pediatric patients with sickle cell disease. JAMA 289:1136–1142

    Article  Google Scholar 

  72. Morris CR, Kuypers FA, Larkin S et al. (2000) Arginine therapy: a novel strategy to induce nitric oxide production in sickle cell disease. Br J Haematol 111:498–500

    Article  Google Scholar 

  73. Serirom S, Raharjo WH, Chotivanich K et al. (2003) Anti-adhesive effect of nitric oxide on Plasmodium falciparum cytoadherence under flow. Am J Pathol 162:1651–1660

    Google Scholar 

  74. Shore AC (2000) Capillaroscopy and the measurement of capillary pressure. Br J Clin Pharmacol 50:501–513

    Article  Google Scholar 

  75. Ince C (2005) The microcirculation is the motor of sepsis. Crit Care 9:S13–S19

    Article  Google Scholar 

  76. Menger MD, Laschke MW, Amon M et al. (2003) Experimental models to study microcirculatory dysfunction in muscle ischemia-reperfusion and osteomyocutaneous flap transfer. Langenbecks Arch Surg 388:281–290

    Article  Google Scholar 

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Keymel, S., Kelm, M., Kleinbongard, P. (2008). Nitric Oxide in the Vascular System: Meet a Challenge. In: Artmann, G., Chien, S. (eds) Bioengineering in Cell and Tissue Research. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-75409-1_18

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  • DOI: https://doi.org/10.1007/978-3-540-75409-1_18

  • Publisher Name: Springer, Berlin, Heidelberg

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