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Nitric Oxide

Synthesis and Metabolism, Tissue Stores, and the Relationship of Endothelium-Derived Nitric Oxide to Endothelium-Dependent Hyperpolarization

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Signal Transduction and the Gasotransmitters

Summary

Nitric oxide (NO) is a gas that was first shown to be synthesized by endothelial cells and macrophages but was subsequently shown to be synthesized by most if not all cell types, including neuronal tissue. NO plays important functions as a signaling substance in mammalian and nonmammalian species. Despite the simple nature of the molecule, the chemistry of NO and its adjuncts have proved to be quite complex and its cellular actions are now known to extend beyond a role as a short-lived cell-signaling substance. This chapter discusses the physiochemical characteristics of NO and nitrosothiols; measurement of NO; metabolic pathways for NO; synthesis of NO; and the important question of whether tissues can store NO, possibly as a nitrosothiol, in astable form. In addition, we discuss the relationship ofNO to another important, but still putative, mediator termed endothelium-derived hyperpolarizing factor.

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References

  1. Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 1980;288(5789):373–376.

    Article  PubMed  CAS  Google Scholar 

  2. Palmer RM, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 1987;327(6122):524–526.

    Article  PubMed  CAS  Google Scholar 

  3. Martinez A. Nitric oxide synthase in invertebrates. Histochem J 1995;27(10):770–776.

    PubMed  CAS  Google Scholar 

  4. Feelisch M. The biochemical pathways of nitric oxide formation from nitrovasodilators: appropriate choice of exogenous NO donors and aspects of preparation and handling of aqueous NO solutions. J Cardiovasc Pharmacol 1991;17:S25-S33.

    Article  CAS  Google Scholar 

  5. Schwartz SE, White WH. Kinetics of reactive dissolutions of nitrogen oxides into aqueous solutions. In: Trace Atmospheric Constituents: Properties, Transformation and Fates. (Schwartz SE, ed.) John Wiley: New York, 1983, pp. 1–17.

    Google Scholar 

  6. Ford PC, Wink DA, Stanbury DM. Autoxidation kinetics of aqueous nitric oxide. FEBS Lett 1993; 326(1–3):1–3.

    Article  PubMed  CAS  Google Scholar 

  7. Kelm M., Yoshida K. Metabolic fate of nitric oxide and related N-oxides. In: Feelisch MSJ, ed. Methods in Nitric Oxide Research. John Wiley: West Sussex, 1996, pp. 47–58.

    Google Scholar 

  8. Kelm M. Nitric oxide metabolism and breakdown. Biochim Biophys Acta 1999;1411(2–3):273–289.

    PubMed  CAS  Google Scholar 

  9. Wink DA, Mitchell JB. Chemical biology of nitric oxide: insights into regulatory, cytotoxic, and cytoprotective mechanisms of nitric oxide. Free Radic Biol Med 1998;25(4–5):434–456.

    Article  PubMed  CAS  Google Scholar 

  10. Grube R., Kelm M, Motz W, et al. Measurement of nitric oxide in biological fluids: implication for in vivo studies. In: The Biology of Nitric Oxide. (Moncada S, ed.) Portland Press: London, 1994, pp. 201–204.

    Google Scholar 

  11. Kelm M, Schrader J. Control of coronary vascular tone by nitric oxide. Circ Res 1990;66(6):1561–1575.

    Article  PubMed  CAS  Google Scholar 

  12. Borland C, Demoncheaux E, Constable E. A chemiluminescent method for studying the reactions of nitric oxide with biologically important molecules in aqueous liquids. In: The Biology of Nitric Oxide. (Feelisch M, Busse R, Higgs EA, eds.) Portland Press: London, 1994, pp. 212–215.

    Google Scholar 

  13. Kharitonov VG, Sundquist AR, Sharma VS. Kinetics of nitric oxide autoxidation in aqueous solution. J Biol Chem 1994;269(8):5881–5883.

    PubMed  CAS  Google Scholar 

  14. Kelm M, Feelisch M, Spahr R, et al. Quantitative and kinetic characterization of nitric oxide and EDRF released from cultured endothelial cells. Biochem Bionhys Res Commun 1988;154(1):236–244.

    Article  CAS  Google Scholar 

  15. Liu Z, Rudd MA, Freedman JE, et al. S-Transnitrosation reactions are involved in the metabolic fate and biological actions of nitric oxide. J Pharmacol Exp Ther 1998;284(2):526–534.

    PubMed  CAS  Google Scholar 

  16. Huie RE, Padmaja S. The reaction of NO with superoxide. Free Radic Res Commun 1993;18(4):195–199.

    Article  PubMed  CAS  Google Scholar 

  17. Wink DA, Miranda KM, Espey MG, et al. Balancing nitric oxide with oxidative and nitrosative stress. In: Mayer B, ed. Springer-Verlag: New York, 2000, pp. 7–24.

    Google Scholar 

  18. Griendling KK, Sorescu D, Ushio-Fukai M. NAD(P)H oxidase: role in cardiovascular biology and disease. Circ Res 2000;86(5):494–501.

    Article  PubMed  CAS  Google Scholar 

  19. Babior BM. NADPH oxidase: an update. Blood 1999;93(5):1464–1476.

    PubMed  CAS  Google Scholar 

  20. Suzuki H, DeLano FA, Parks DA, et al. Xanthine oxidase activity associated with arterial blood pressure in spontaneously hypertensive rats. Proc Natl Acad Sci USA 1998;95(8):4754–4759.

    Article  PubMed  CAS  Google Scholar 

  21. Fleming I, Michaelis UR, Bredenkotter D, et al. Endothelium-derived hyperpolarizing factor synthase (Cytochrome P450 2C9) is a functionally significant source of reactive oxygen species in coronary arteries. Circ Res 2001;88(1):44–51.

    Article  PubMed  CAS  Google Scholar 

  22. Cosentino F, Sill JC, Katusic ZS. Role of superoxide anions in the mediation of endothelium-dependent contractions. Hypertension 1994;23(2):229–235.

    Article  PubMed  CAS  Google Scholar 

  23. Xia Y, Tsai AL, Berka V, et al. Superoxide generation from endothelial nitric-oxide synthase: a Ca2+/calmodulin-dependent and tetrahydrobiopterin regulatory process. J Biol Chem 1998;273(40):25804–25808.

    Article  PubMed  CAS  Google Scholar 

  24. Koppenol WH, Moreno JJ, Pryor WA, et al. Peroxynitrite, a cloaked oxidant formed by nitric oxide and superoxide. Chem Res Toxicol 1992;5(6):834–842.

    Article  PubMed  CAS  Google Scholar 

  25. Stadler J, Billiar TR, Curran RD, et al. Effect of exogenous and endogenous nitric oxide on mitochondrial respiration of rat hepatocytes. Am J Physiol 1991;260(5 pt 1):C910-C916.

    PubMed  CAS  Google Scholar 

  26. Nguyen T, Brunson D, Crespi CL, et al. DNA damage and mutation in human cells exposed to nitric oxide in vitro. Proc Natl Acad Sci USA 1992;89(7):3030–3034.

    Article  PubMed  CAS  Google Scholar 

  27. Beckman JS, Beckman TW, Chen J, et al. Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci USA 1990;87(4):1620–1624.

    Article  PubMed  CAS  Google Scholar 

  28. Liu S, Beckman JS, Ku DD. Peroxynitrite, a product of superoxide and nitric oxide, produces coronary vasorelaxation in dogs. J Pharmacol Exp Ther 1994;268(3):1114–1121.

    PubMed  CAS  Google Scholar 

  29. Wu M, Pritchard KA Jr., Kaminski PM, et al. Involvement of nitric oxide and nitrosothiols in relaxation of pulmonary arteries to peroxynitrite. Am J Physiol 1994;266(5 pt 2):H2108-H2113.

    PubMed  CAS  Google Scholar 

  30. Mayer B, Schrammel A, Klatt P, et al. Peroxynitrite-induced accumulation of cyclic GMP in endothelial cells and stimulation of purified soluble guanylyl cyclase: dependence on glutathione and possible role of 5-nitrosation. J Biol Chem 1995;270(29):17355–17360.

    Article  PubMed  CAS  Google Scholar 

  31. Mayer B, Pfeiffer S, Schrammel A, et al. A new pathway of nitric oxide/cyclic GMP signaling involving S-nitrosoglutathione. J Biol Chem 1998;273(6):3264–3270.

    Article  PubMed  CAS  Google Scholar 

  32. Tarpey MM, Beckman JS, Ischiropoulos H, et al. Peroxynitrite stimulates vascular smooth muscle cell cyclic GMP synthesis. FEBS Lett 1995;364(3):314–318.

    Article  PubMed  CAS  Google Scholar 

  33. Moro MA, Darley-Usmar VM, Goodwin DA, et al. Paradoxical fate and biological action of peroxynitrite on human platelets. Proc Nat! Acad Sci USA 1994;91(14):6702–6706.

    Article  CAS  Google Scholar 

  34. Lefer DJ, Scalia R, Campbell B, et al. Peroxynitrite inhibits leukocyte-endothelial cell interactions and protects against ischemia-reperfusion injury in rats. J Clin Invest 1997;99(4):684–691.

    Article  PubMed  CAS  Google Scholar 

  35. Nakamura M, Thourani VH, Ronson RS, et al. Glutathione reverses endothelial damage from peroxynitrite, the byproduct of nitric oxide degradation, in crystalloid cardioplegia. Circulation 2000;102(19 Suppl 3):111332–111338.

    Google Scholar 

  36. Cheung PY, Wang W, Schulz R. Glutathione protects against myocardial ischemia-reperfusion injury by detoxifying peroxynitrite. J Mol Cell Cardiol 2000:32(9):1669–1678.

    Article  PubMed  CAS  Google Scholar 

  37. Ma XL, Gao F, Lopez BL, et al. Peroxynitrite, a two-edged sword in post-ischemic myocardial injurydichotomy of action in crystal. J Pharmacol Exp Ther 2000;292(3):912–920.

    PubMed  CAS  Google Scholar 

  38. Moncada S, Palmer RM, Higgs EA. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev 1991;43(2):109–142.

    PubMed  CAS  Google Scholar 

  39. Ignarro L. Biosynthesis and metabolism of endothelium-derived nitric oxide. Annu Rev Pharmacol Toxicol 1990;30:535–560.

    Article  PubMed  CAS  Google Scholar 

  40. Beckman JS. The physiological and pathological chemistry of nitric oxide. In: Lancaster J Jr., ed. Nitric Oxide: Principles and Actions. Academic: San Diego, 1996, pp. 1–71.

    Google Scholar 

  41. Wennmalm A, Benthin G, Petersson AS. Dependence of the metabolism of nitric oxide (NO) in healthy human whole blood on the oxygenation of its red cell haemoglobin. Br J Pharmacol 1992;106(3):507,508.

    Article  PubMed  CAS  Google Scholar 

  42. Stamler JS, Jia L, Eu JP, et al. Blood flow regulation by S-nitrosohemoglobin in the physiological oxygen gradient. Science 1997;276(5321):2034–2037.

    Article  PubMed  CAS  Google Scholar 

  43. Jia L, Bonaventura C, Bonaventura J, et al. S-nitrosohaemoglobin: a dynamic activity of blood involved in vascular control. Nature 1996;380(6571):221–226.

    Article  PubMed  CAS  Google Scholar 

  44. Gow AJ, Stamler JS. Reactions between nitric oxide and haemoglobin under physiological conditions. Nature 1998;391(6663):169–173.

    Article  PubMed  CAS  Google Scholar 

  45. Lancaster JR Jr. Simulation of the diffusion and reaction of endogenously produced nitric oxide. Proc Natl Acad Sci USA 1994;91(17):8137–8141.

    Article  PubMed  CAS  Google Scholar 

  46. Hobbs AJ, Gladwin MT, Patel RP, et al. Haemoglobin: NO transporter, NO inactivator or None of the above? Trends Pharmacol Sci 2002;23(9):406–411.

    Article  PubMed  CAS  Google Scholar 

  47. Ignarro LJ, Buga GM, Wood KS, et al. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci USA 1987;84(24):9265–9269.

    Article  PubMed  CAS  Google Scholar 

  48. Gow AJ, Luchsinger BP, Pawloski JR, et al. The oxyhemoglobin reaction of nitric oxide. Proc Natl Acad Sci USA 1999;96(16):9027–9032.

    Article  PubMed  CAS  Google Scholar 

  49. Pawloski JR, Hess DT, Stamler JS. Export by red blood cells of nitric oxide bioactivity. Nature 2001;409(6820):622–626.

    Article  PubMed  CAS  Google Scholar 

  50. Patel RP, Hogg N, Spencer NY, et al. Biochemical characterization of human Snitrosohemoglobin: effects on oxygen binding and transnitrosation. J Biol Chem 1999;274(22):15487–15492.

    Article  PubMed  CAS  Google Scholar 

  51. Wolzt M, MacAllister RJ, Davis D, et al. Biochemical characterization of S-nitrosohemoglobin: mechanisms underlying synthesis, NO release, and biological activity. J Biol Chem 1999;274(41): 28983–28990.

    Article  PubMed  CAS  Google Scholar 

  52. Clancy RM, Miyazaki Y, Cannon PJ. Use of thionitrobenzoic acid to characterize the stability of nitric oxide in aqueous solutions and in porcine aortic endothelial cell suspensions. Anal Biochem 1990;191(1):138–143.

    Article  PubMed  CAS  Google Scholar 

  53. Hogg N, Singh RJ, Kalyanaraman B. The role of glutathione in the transport and catabolism of nitric oxide. FEBS Lett 1996;382(3):223–228.

    Article  PubMed  CAS  Google Scholar 

  54. Pryor WA, Church DF, Govindan CK, et al. Oxidation of thiols by nitric oxide and nitrogen dioxide synthetic utility and toxicological implications. J Org Chem 1982;47:159–161.

    Article  Google Scholar 

  55. Tamir S, Tannenbaum SR. The role of nitric oxide (NO) in the carcinogenic process. Biochim Biophys Acta 1996;1288(2):F31-F36.

    PubMed  Google Scholar 

  56. Bonner FT, Stedman G. The chemistry of nitric oxide and redox-related species. In: Feelisch MSJ, ed. Methods in Nitric Oxide Research. John Wiley: West Sussex, 1996, pp. 3–18.

    Google Scholar 

  57. Kharitonov VG, Sundquist AR, Sharma VS. Kinetics of nitrosation of thiols by nitric oxide in the presence of oxygen. J Biol Chem 1995;270(47):28158–28164.

    Article  PubMed  CAS  Google Scholar 

  58. Stamler JS, Singel DJ, Loscalzo J. Biochemistry of nitric oxide and its redox-activated forms. Science 1992;258(5090):1898–1902.

    Article  PubMed  CAS  Google Scholar 

  59. Stamler JS, Simon DI, Osborne JA, et al. S-nitrosylation of proteins with nitric oxide: synthesis and characterization of biologically active compounds. Proc Natl Acad Sci USA 1992;89(1):444–448.

    Article  PubMed  CAS  Google Scholar 

  60. Butler AR, Flitney FW, Williams DL. NO, nitrosonium ions, nitroxide ions, nitrosothiols and ironnitrosyls in biology: a chemist’s perspective. Trends Pharmacol Sci 1995;16(1):18–22.

    Article  PubMed  CAS  Google Scholar 

  61. Myers PR, Minor RL Jr, Guerra R Jr, et al. Vasorelaxant properties of the endothelium-derived relaxing factor more closely resemble S-nitrosocysteine than nitric oxide. Nature 1990;345(6271):161–163.

    Article  PubMed  CAS  Google Scholar 

  62. Rubanyi GM, Vanhoutte PM. Oxygen-derived free radicals, endothelium, and responsiveness of vascular smooth muscle. Am J Physiol 1986;250(5 pt 2):H815-H821.

    PubMed  CAS  Google Scholar 

  63. Keaney JF Jr, Simon DI, Stamler JS, et al. NO forms an adduct with serum albumin that has endothelium-derived relaxing factor-like properties. J Clin Invest 1993;91(4):1582–1589.

    Article  PubMed  CAS  Google Scholar 

  64. Stamler JS, Jaraki O, Osborne J, et al. Nitric oxide circulates in mammalian plasma primarily as an S-nitroso adduct of serum albumin. Proc Natl Acad Sci USA 1992;89(16):7674–7677.

    Article  PubMed  CAS  Google Scholar 

  65. Radomski MW, Rees DD, Dutra A, et al. S-nitroso-glutathione inhibits platelet activation in vitro and in vivo. Br J Pharmacol 1992;107(3):745–749.

    Article  PubMed  CAS  Google Scholar 

  66. Marley R, Feelisch M, Holt S, et al. A chemiluminescense-based assay for S-nitrosoalbumin and other plasma S-nitrosothiols. Free Radic Res 2000;32(1):1–9.

    Article  PubMed  CAS  Google Scholar 

  67. Gaston B. Nitric oxide and thiol groups. Biochim Biophys Acta 1999;1411(2–3):323–333.

    Google Scholar 

  68. Beckman JS, Koppenol WH. Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am J Physiol 1996;271(5 pt 1):C1424-C1437.

    Google Scholar 

  69. Nedospasov A, Rafikov R, Beda N, et al. An autocatalytic mechanism of protein nitrosylation. Proc Natl Acad Sci USA 2000;97(25):13,543–13,548.

    Article  CAS  Google Scholar 

  70. Hogg N. Biological chemistry and clinical potential of S-nitrosothiols. Free Radic Biol Med 2000 28:1478–1486.

    Article  PubMed  CAS  Google Scholar 

  71. Hughes MN. Relationships between nitric oxide, nitroxyl ion, nitrosonium cation and peroxynitrite. Biochim Biophys Acta 1999;1411(2–3):263–272.

    PubMed  CAS  Google Scholar 

  72. Pino RZ, Feelisch M. Bioassay discrimination between nitric oxide (NO) and nitroxyl (NO-) using L-cysteine. Biochem Biophys Res Commun 1994;201(1):54–62.

    Article  PubMed  CAS  Google Scholar 

  73. Zamora R, Grzesiok A, Weber H, et al. Oxidative release of nitric oxide accounts tor guanylylcyclase stimulating, vasodilator and anti-platelet activity of Piloty’s acid: a comparison with Angeli’ s salt. Biochem J 1995;312 (pt 2):333–339.

    PubMed  CAS  Google Scholar 

  74. Doyle MP, Mahapatro SN, Broene RD, et al. Oxidation and reduction of hemoproteins by trioxodinitrate(II): the role of nitrosyl hydride and nitrite. J Am Chem Soc 1988;110:593–599.

    Article  CAS  Google Scholar 

  75. Feelisch M, TePoel PM, Zamora R, et al. Understanding the controversy over the identity of EDRF. Nature 1994;368(6466):62–65.

    Article  PubMed  CAS  Google Scholar 

  76. Khan AA, Schuler MM, Coppock RW. Inhibitory effects of various sulfur compounds on the activity of bovine erythrocyte enzymes. J Toxicol Environ Health 1987;22(4):481–490.

    Article  PubMed  CAS  Google Scholar 

  77. Andrews KL, Triggle CR, Ellis A. NO and the vasculature: where does it come from and what does it do? Heart Fail Rev 2002;7(4):423–445.

    Article  PubMed  CAS  Google Scholar 

  78. Koppenol WH. Thermodynamics of reactions involving nitrogen-oxygen compounds. Methods Enzymol 1996;268:7–12.

    Article  PubMed  CAS  Google Scholar 

  79. Li CG, Karagiannis J, Rand MJ. Comparison of the redox forms of nitrogen monoxide with the nitrergic transmitter in the rat anococcygeus muscle. Br J Pharmacol 1999;127(4):826–834.

    Article  PubMed  CAS  Google Scholar 

  80. Dierks EA, Burstyn JN. Nitric oxide (NO), the only nitrogen monoxide redox form capable of activating soluble guanylyl cyclase. Biochem Pharmacol 1996;51(12):1593–1600.

    Article  PubMed  CAS  Google Scholar 

  81. Schmidt HH, Hofmann H, Schindler U, et al. No NO from NO synthase. Proc Natl Acad Sci USA 1996;93(25): 14,492–14,497.

    Article  CAS  Google Scholar 

  82. Adak S, Wang Q, Stuehr DJ. Arginine conversion to nitroxide by tetrahydrobiopterin-free neuronal nitric-oxide synthase: implications for mechanism. J Biol Chem 2000;275(43):33,554–33,561.

    Google Scholar 

  83. Hogg N. The biochemistry and physiology of S-nitrosothiols. Annu Rev Pharmacol Toxicol 2002;42:585–600.

    Article  PubMed  CAS  Google Scholar 

  84. Arnelle DR, Stamler JS. NO+, NO, and NO- donation by S-nitrosothiols: implications for regulation of physiological functions by S-nitrosylation and acceleration of disulfide formation. Arch Biochem Biophys 1995;318(2):279–285.

    Article  PubMed  CAS  Google Scholar 

  85. Fukuto JM, Chiang K, Hszieh R, et al. The pharmacological activity of nitroxyl: a potent vasodilator with activity similar to nitric oxide and/or endothelium-derived relaxing factor. J Pharmacol Exp Ther 1992:263(2):546–551.

    PubMed  CAS  Google Scholar 

  86. Pufahl RA, Wishnok JS, Marletta MA. Hydrogen peroxide-supported oxidation of NG-hydroxy-L-arginine by nitric oxide synthase. Biochemistry 1995;34(6):1930–1941.

    Article  PubMed  CAS  Google Scholar 

  87. Wong PS, Hyun J, Fukuto JM, et al. Reaction between S-nitrosothiols and thiols: generation of nitroxyl (HNO) and subsequent chemistry. Biochemistry 1998;37(16):5362–5371.

    Article  PubMed  CAS  Google Scholar 

  88. Bartberger MD, Liu W, Ford E, et al. The reduction potential of nitric oxide (NO) and its importance to NO biochemistry. Proc Natl Acad Sci USA 2002;99(17):10958–10963.

    Article  PubMed  CAS  Google Scholar 

  89. Fukuto JM, Wallace GC, Hszieh R, et al. Chemical oxidation of N-hydroxyguanidine compounds: release of nitric oxide, nitroxyl and possible relationship to the mechanism of biological nitric oxide generation. Biochem Pharmacol 1992;43(3):607–613.

    Article  PubMed  CAS  Google Scholar 

  90. Murphy ME, Sies H. Reversible conversion of nitroxyl anion to nitric oxide by superoxide dismutase. Proc Natl Acad Sci USA 1991;88(23):10,860–10,864.

    Article  CAS  Google Scholar 

  91. Kim WK, Choi YB, Rayudu PV, et al. Attenuation of NMDA receptor activity and neurotoxicity by nitroxyl anion, NO-. Neuron 1999;24(2):461–469.

    Article  PubMed  CAS  Google Scholar 

  92. Ma XL, Gao F, Liu GL, et al. Opposite effects of nitric oxide and nitroxyl on postischemic myocardial injury. Proc Nat! Acad Sci USA 1999;96(25):14,617–14,622.

    Article  CAS  Google Scholar 

  93. Paolocci N, Saavedra WF, et al. Nitroxyl anion exerts redox-sensitive positive cardiac inotropy in vivo by calcitonin gene-related peptide signaling. Proc Nat Acad Sci USA 2001;98(18):10,463–10,468.

    Article  CAS  Google Scholar 

  94. Paolocci N, Katori T, Champion HC, etal. Positive inotropic and lusitropic effects of HNO/NO- in failing hearts: independence from beta-adrenergic signaling. Proc Natl Acad Sci USA 2003;100(9):5537–5542.

    Article  PubMed  CAS  Google Scholar 

  95. Miranda KM, Nims RW, Thomas DD, et al. Comparison of the reactivity of nitric oxide and nitroxyl with heme proteins: a chemical discussion of the differential biological effects of these redox related products of NOS. J Inorg Biochem 2003;93(1–2):52–60.

    Article  PubMed  CAS  Google Scholar 

  96. Hobbs AJ. Soluble guanylate cyclase: the forgotten sibling. Trends Pharmacol Sci 199718:484–491.

    Google Scholar 

  97. Ellis A, Li CG, Rand MJ. Differential actions of L-cysteine on responses to nitric oxide, nitroxyl anions and EDRF in the rat aorta. Br J Pharmacol 2000;129:315–322.

    Article  PubMed  CAS  Google Scholar 

  98. Wanstall JC, Jeffery TK, Gambino A, et al. Vascular smooth muscle relaxations mediated by nitric oxide donors: a comparison with acetylcholine, nitric oxide and nitroxyl ion. Br J Pharmacol 2001;134:463–472.

    Article  PubMed  CAS  Google Scholar 

  99. Reif A, Zecca L, Riederer P, et al. Nitroxyl oxidizes NADPH in a superoxide dismutase inhibitable manner. Free Radic Biol Med 2001;30(7):803–808.

    Article  PubMed  CAS  Google Scholar 

  100. Thomas G, Ramwell PW. Vascular relaxation mediated by hydroxylamines and oximes: their conversion to nitrites and mechanism of endothelium dependent vascular relaxation. Biochem Biophys Res Commun 1989;164(2):889–893.

    Article  PubMed  CAS  Google Scholar 

  101. DeMaster EG, Raij L, Archer SL, et al. Hydroxylamine is a vasorelaxant and a possible intermediate in the oxidative conversion of L-arginine to nitric oxide. Biochem Biophys Res Commun 1989;163(1): 527–533.

    Article  PubMed  CAS  Google Scholar 

  102. Huang Y. Hydroxylamine-induced relaxation inhibited by K+ channel blockers in rat aortic rings. Eur J Pharmacol 1998;349(1):53–60.

    Article  PubMed  CAS  Google Scholar 

  103. Craven PA, DeRubertis FR, Pratt DW. Electron spin resonance study of the role of NO catalase in the activation of guanylate cyclase by NaN3 and NH2OH: modulation of enzyme responses by heme proteins and their nitrosyl derivatives. J Biol Chem 1979;254(17):8213–8222.

    PubMed  CAS  Google Scholar 

  104. Correia NA, Oliveira RB, Ballejo G. Pharmacological profile of nitrergic nerve-, nitric oxide-, nitrosoglutath. Life Sci 2000;68(6):709–717.

    Article  PubMed  CAS  Google Scholar 

  105. Bates JN, Harrison DG, Myers PR, et al. EDRF: nitrosylated compound or authentic nitric oxide. Basic Res Cardiol 1991;86(Suppl 2):17–26.

    PubMed  Google Scholar 

  106. Thornbury KD, Ward SM, Dalziel HH, et al. Nitric oxide and nitrosocysteine mimic nonadrenergic, noncholinergic hyperpolarization in canine proximal colon. Am J Physiol 1991;261(3 pt 1): G553-G557.

    PubMed  CAS  Google Scholar 

  107. Liu X, Gillespie JS, Martin W. Non-adrenergic, non-cholinergic relaxation of the bovine retractor penis muscle: role of S-nitrosothiols. Br J Pharmacol 1994;111(4):1287–1295.

    Article  PubMed  CAS  Google Scholar 

  108. Muller B, Kleschyov AL, Alencar JL, et al. Nitric oxide transport and storage in the cardiovascular system. Ann NY Acad Sci 2002;962:131–139.

    Article  PubMed  CAS  Google Scholar 

  109. Rodriguez J, Maloney RE, Rassaf T, et al. Chemical nature of nitric oxide storage forms in rat vascular tissue. Proc Natl Acad Sci USA 2003;100(1):336–341.

    Article  PubMed  CAS  Google Scholar 

  110. Davisson RL, Travis MD, Bates JN, et al. Stereoselective actions of S-nitrosocysteine in central nervous system of conscious rats. Am J Physiol 1997;272(5 pt 2):H2361-H2368.

    PubMed  CAS  Google Scholar 

  111. Al Sa’doni HH, Megson IL, Bisland S, et al. Neocuproine, a selective Cu(I) chelator, and the relaxation of rat vascular smooth muscle by S-nitrosothiols. Br J Pharmacol 1997;121(6):1047–1050.

    Article  Google Scholar 

  112. McMahon TJ, Moon RE, Luschinger BP, et al. Nitric oxide in the human respiratory cycle. Nat Med 2002;8(7):711–717.

    PubMed  CAS  Google Scholar 

  113. Arnelle DR, Day BJ, Stamler JS. Diethyl dithiocarbamate-induced decomposition of S-nitrosothiols. Nitric Oxide 1997;1(1):56–64.

    Article  PubMed  CAS  Google Scholar 

  114. Scorza G, Pietraforte D, Minetti M. Role of ascorbate and protein thiols in the release of nitric oxide from S-nitroso-albumin and S-nitroso-glutathione in human plasma. Free Radic Biol Med 1997;22(4):633–642.

    Article  PubMed  CAS  Google Scholar 

  115. Aleryani S, Milo E, Rose Y, et al. Superoxide-mediated decomposition of biological S-nitrosothiols. J Biol Chem 1998;273(11):6041–6045.

    Article  PubMed  CAS  Google Scholar 

  116. Choi YB, Tenneti L, Le DA, et al. Molecular basis of NMDA receptor-coupled ion channel modulation by S-nitrosylation. Nat Neurosci 2000;3(1):15–21.

    Article  PubMed  CAS  Google Scholar 

  117. Favre CJ, Ufret-Vincenty CA, Stone MR, et al. Ca2+ pool emptying stimulates Ca2+ entry activated by S-nitrosylation. J Biol Chem 1998;273(47):30,855–30,858.

    Article  CAS  Google Scholar 

  118. Renganathan M, Cummins TR, Waxman SG. Nitric oxide blocks fast, slow, and persistent Na+ channels in C-type DRG neurons by 5-nitrosylation. J Neurophysiol 2002;87(2):761–775.

    PubMed  CAS  Google Scholar 

  119. Sun J, Xu L, Eu JP, et al. Nitric oxide, NOC-12, and S-nitrosoglutathione modulate the skeletal muscle calcium release channel/ryanodine receptor by different mechanisms: an allosteric function for 02 in S-nitrosylation of the channel. J Biol Chem 2003;278(10):8184–8189.

    Article  PubMed  CAS  Google Scholar 

  120. Bauer PM, Buga GM, Fukuto JM, et al. Nitric oxide inhibits ornithine decarboxylase via 5-nitrosylation of cysteine 360 in the active site of the enzyme. J Biol Chem 2001;276(37):34,458–34,464.

    Article  CAS  Google Scholar 

  121. Padgett CM, Whorton AR. S-nitrosoglutathione reversibly inhibits GAPDH by S-nitrosylation. Am J Physiol 1995;269(3 pt 1):C739-C749.

    PubMed  CAS  Google Scholar 

  122. Perez-Mato I, Castro C, Ruiz FA, et al. Methionine adenosyltransferase S-nitrosylation is regulated by the basic and acidic amino acids surrounding the target thiol. J Biol Chem 1999;274(24): 17,075–17,079.

    Article  CAS  Google Scholar 

  123. Stamler JS, Toone EJ, Lipton SA, et al. (S)NO signals: translocation, regulation, and a consensus motif. Neuron 1997;18(5):691–696.

    Article  PubMed  CAS  Google Scholar 

  124. Ascenzi P, Colasanti M, Persichini T, et al. Re-evaluation of amino acid sequence and structural consensus rules for cysteine-nitric oxide reactivity. Biol Chem 2000;381(7):623–627.

    Article  PubMed  CAS  Google Scholar 

  125. Vanin AF. Endothelium-derived relaxing factor is a nitrosyl iron complex with thiol ligands. FEBS Lett 1991;289(1):1–3.

    Article  PubMed  CAS  Google Scholar 

  126. Vedernikov YP, Mordvintcev PI, Malenkova IV, et al. Similarity between the vasorelaxing activity of dinitrosyl iron cysteine complexes and endothelium-derived relaxing factor. Eur J Pharmacol 1992;211(3):313–317.

    Article  PubMed  CAS  Google Scholar 

  127. Vanin AF, Mordvintcev PI, Hauschildt S, et al. The relationship between L-arginine-dependent nitric oxide synthesis, nitrite release and dinitrosyl-iron complex formation by activated macrophages. Biochim Biophys Acta 1993;1177(1):37–42.

    Article  PubMed  CAS  Google Scholar 

  128. Ueno T, Suzuki Y, Fujii S, et al. In vivo nitric oxide transfer of a physiological NO carrier, dinitrosyl dithiolato iron complex, to target complex. Biochem Pharmacol 2002;63(3):485–493.

    Article  PubMed  CAS  Google Scholar 

  129. Muller B, Kleschyov AL, Stoclet JC. Evidence for N-acetylcysteine-sensitive nitric oxide storage as dinitrosyl-iron complexes in lipopolysaccharide-treated rat aorta. Br J Pharmacol 1996;119(6): 1281–1285.

    Article  PubMed  CAS  Google Scholar 

  130. Gillham JC, Kenny LC, Baker PN. An overview of endothelium-derived hyperpolarising factor (EDHF) in normal and compromised pregnancies. Eur J Obstet Gynecol Reprod Biol 2003;109(1):2–7.

    Article  PubMed  CAS  Google Scholar 

  131. Malinski T, Taha Z. Nitric oxide release from a single cell measured in situ by a porphyrinic-based microsensor. Nature 1992;358(6388):676–678.

    Article  PubMed  CAS  Google Scholar 

  132. Ledo A, Barbosa RM, Frade J, et al. Nitric oxide monitoring in hippocampal brain slices using electrochemical methods. Methods Enzymol 2002;359:111–125.

    Article  PubMed  CAS  Google Scholar 

  133. Allen BW, Coury LA Jr, Piantadosi CA. Electrochemical detection of physiological nitric oxide: materials and methods. Methods Enzymol 2002;359:125–134.

    Article  PubMed  CAS  Google Scholar 

  134. Freedman JE, Loscalzo J, Barnard MR, et al. Nitric oxide released from activated platelets inhibits platelet recruitment. J Clin Invest 1997;100(2):350–356.

    Article  PubMed  CAS  Google Scholar 

  135. Malinski T, Mesaros S, Patton SR, et al. Direct measurement of nitric oxide in the cardiovascular system. Physiol Res 1996;45(4):279–284.

    PubMed  CAS  Google Scholar 

  136. Ellis A, Lu H, Li CG, et al. Effects of agents that inactivate free radical NO (NO*) on nitroxyl anionmediated relaxations, and on the detection of NO* released from the nitroxyl anion donor Angeli’ s salt. Br J Pharmacol 2001;134(3):521–528.

    Article  PubMed  CAS  Google Scholar 

  137. Guo JP, Murohara T, Buerke M, et al. Direct measurement of nitric oxide release from vascular endothelial cells. J Appl Physiol 1996;81(2):774–779.

    PubMed  CAS  Google Scholar 

  138. Liu ZG, Ge ZD, He GW. Difference in endothelium-derived hyperpolarizing factor-mediated hyperpolarization and nitric oxide release between human internal mammary artery and saphenous vein. Circulation 2000;102(19 suppl 3):111296–111301.

    Google Scholar 

  139. Kojima H, Nakatsubo N, Kikuchi K, et al. Detection and imaging of nitric oxide with novel fluorescent indicators: diaminofluoresceins. Anal Chem 1998;70(13):2446–2453.

    Article  PubMed  CAS  Google Scholar 

  140. Nakatsubo N, Kojima H, Kikuchi K, et al. Direct evidence of nitric oxide production from bovine aortic endothelial cells using new fluorescence indicators: diaminofluoresceins. FEBS Lett 1998;427(2): 263–266.

    Article  PubMed  CAS  Google Scholar 

  141. Kojima H, Nakatsubo N, Kikuchi K, et al. Direct evidence of NO production in rat hippocampus and cortex using a new fluorescent indicator: DAF-2 DA. Neuroreport 1998;9(15):3345–3348.

    Article  PubMed  CAS  Google Scholar 

  142. Broillet M, Randin O, Chatton J. Photoactivation and calcium sensitivity of the fluorescent NO indicator 4,5-diaminofluorescein (DAF-2): implications for cellular NO imaging. FEBS Lett 2001;491(3):227–232

    Article  PubMed  CAS  Google Scholar 

  143. Espey MG, Miranda KM, Thomas DD, et al. Distinction between nitrosating mechanisms within human cells and aqueous solution. J Biol Chem 2001;276(32):30,085–30,091.

    Article  CAS  Google Scholar 

  144. Jourd’heuil D. Increased nitric oxide-dependent nitrosylation of 4,5-diaminofluorescein by oxidants: implications for the measurement of intracellular nitric oxide. Free Radic Biol Med 2002;33(5):676–684

    Article  PubMed  Google Scholar 

  145. Nagata N, Momose K, Ishida Y. Inhibitory effects of catecholamines and anti-oxidants on the fluorescence reaction of 4,5-diaminofluorescein, DAF-2, a novel indicator of nitric oxide. J Biochem (Tokyo) 1999;125(4):658–661.

    Article  CAS  Google Scholar 

  146. Leikert JF, Rathel TR, Muller C, et al. Reliable in vitro measurement of nitric oxide released from endothelial cells using low concentrations of the fluorescent probe 4,5-diaminofluorescein. FEBS Lett 2001;506(2):131–134.

    Article  PubMed  CAS  Google Scholar 

  147. Marzinzig M, Nussler AK, Stadler J, et al. Improved methods to measure end products of nitric oxide in biological fluids: nitrite, nitrate, and S-nitrosothiols. Nitric Oxide 1997;1(2):177–189.

    Article  PubMed  CAS  Google Scholar 

  148. MacMicking J, Xie QW, Nathan C. Nitric oxide and macrophage function. Annu Rev Immunol 1997;15:323–350.

    Article  PubMed  CAS  Google Scholar 

  149. Scharfstein JS, Keaney JF Jr, Slivka A, et al. In vivo transfer of nitric oxide between a plasma proteinbound reservoir and low molecular weight thiols. J Clin Invest 1994;94(4):1432–1439.

    Article  PubMed  CAS  Google Scholar 

  150. Minamiyama Y, Takemura S, Inoue M. Effect of thiol status on nitric oxide metabolism in the circulation. Arch Biochem Biophys 1997;341(1):186–192.

    Article  PubMed  CAS  Google Scholar 

  151. Goldman RK, Vlessis AA, Trunkey DD. Nitrosothiol quantification in human plasma. Anal Biochem 1998;259(1):98–103.

    Article  PubMed  CAS  Google Scholar 

  152. Jourd’heuil D, Hallen K, Feelisch M, et al. Dynamic state of S-nitrosothiols in human plasma and whole blood. Free Radic Biol Med 2000;28(3):409–417.

    Article  PubMed  Google Scholar 

  153. Rossi R, Giustarini D, Milzani A, et al. Physiological levels of S-nitrosothiols in human plasma. Circ Res 2001;89(12):E47.

    PubMed  CAS  Google Scholar 

  154. Tsikas D, Gutzki FM, Rossa S, et al. Measurement of nitrite and nitrate in biological fluids by gas chromatography-mass spectrometry and by the Griess assay: problems with the Griess assay-solutions by gas chromatography-mass spectrometry. Anal Biochem 1997;244(2):208–220.

    Article  PubMed  CAS  Google Scholar 

  155. Butler AR, Rhodes P Chemistry, analysis, and biological roles of S-nitrosothiols. Anal Biochem 1997;249(1):1–9.

    Article  PubMed  CAS  Google Scholar 

  156. Welch GN, Upchurch GR Jr, Loscalzo J. S-Nitrosothiol detection. Methods Enzymol 1996;268:293–298.

    Article  PubMed  CAS  Google Scholar 

  157. Tsikas D, Sandmann J, Holzberg D, et al. Determination of S-nitrosoglutathione in human and rat plasma by high-performance liquid chromatography with fluorescence and ultraviolet absorbance detection after precolumn derivatization with o-phthalaldehyde. Anal Biochem 1999;273(1):32–40.

    Article  PubMed  CAS  Google Scholar 

  158. Tsikas D, Sandmann J, Gutzki FM, et al. Measurement of S-nitrosoalbumin by gas chromatographymass spectrometry. II. Quantitative determination of S-nitrosoalbumin in human plasma using S-[15N]nitrosoalbumin as internal standard. J Chromatogr 1999;726:13–24.

    Article  CAS  Google Scholar 

  159. Mirza UA, Chait BT, Lander HM. Monitoring reactions of nitric oxide with peptides and proteins by electrospray ionization-mass spectrometry. J Biol Chem 1995;270(29):17,185–17,188.

    CAS  Google Scholar 

  160. Tsikas D, Raida M, Sandmann J, et al. Electrospray ionization mass spectrometry of low-molecularmass S-nitroso compounds and their thiols. J Chromatogr B Biomed Sci Appl 2000;742(1):99–108.

    Article  PubMed  CAS  Google Scholar 

  161. Gaston B, Reilly J, Drazen JM, et al. Endogenous nitrogen oxides and bronchodilator S-nitrosothiols in human airways. Proc Natl Acad Sci USA 1993;90(23):10,957–10,961.

    Article  CAS  Google Scholar 

  162. Stamler JS, Feelisch M. Preparation and detection of S-nitrosothiols. In: Methods in Nitric Oxide Research. (Feelisch M, Stamler JS, ed.) John Wiley: West Sussex, 1996, pp. 522–539.

    Google Scholar 

  163. Saville B. A scheme for the colorimetric determination of microgram amounts of thiols. Analyst 1958;(83):670–672.

    Article  Google Scholar 

  164. Samouilov A, Zweier JL. Development of chemiluminescence-based methods for specific quantitation of nitrosylated thiols. Anal Biochem 1998;258(2):322–330.

    Article  PubMed  CAS  Google Scholar 

  165. Krstulovic AM, Brown PR. Basic theory and terminology. In: Reversed-phase High-Performance Liquid Chromatography: Theory, Practice and Biomedical applications. (Krstulovic AM, Brown PR, ed.) John Wiley: New York, 1982, pp. 4–32.

    Google Scholar 

  166. Pfeiffer S, Schrammel A, Schmidt K, et al. Electrochemical determination of S-nitrosothiols with a Clark-type nitric oxide electrode. Anal Biochem 1998;258(1):68–73.

    Article  PubMed  CAS  Google Scholar 

  167. Tsikas D, Denker K, Frolich JC. Artifactual-free analysis of S-nitrosoglutathione and S-nitroglutathione by neutral-pH, anion-pairing, high-performance liquid chromatrography: study on peroxynitritemediated S-nitration of glutathione to S-nitroglutathione under physiological conditions. J Chromatogr A 2001;915:107–116.

    Article  PubMed  CAS  Google Scholar 

  168. Ng ESM, Jourd’heuil D, McCord JM, et al. S-nitroso-albumin formed from inhaled NO is a physiologic nitric oxide delivery system during ischemia/reperfusion. Circ Res 2004;94(4):559–565.

    Article  PubMed  CAS  Google Scholar 

  169. Rassaf T, Preik M, Kleinbongard P, et al. Evidence for in vivo transport of bioactive nitric oxide in human plasma. J Clin Invest 2002;109(9):1241–1248.

    PubMed  CAS  Google Scholar 

  170. Feelisch M, Rassaf T, Mnaimneh S, et al. Concomitant S-, N-, and heme-nitros(y1)ation in biological tissues and fluids: implications for the fate of NO in vivo. FASEB J 2002;16(13):1775–1785.

    Article  PubMed  CAS  Google Scholar 

  171. Park JK, Kostka P. Fluorometric detection of biological S-nitrosothiols. Anal Biochem 1997;249(1): 61–66.

    Article  PubMed  CAS  Google Scholar 

  172. Wang K, Zhang W, Xian M, et al. New chemical and biological aspects of S-nitrosothiols. Curr Med Chem 2000:7(8):821–834.

    Article  PubMed  CAS  Google Scholar 

  173. Misko TP, Schilling RJ, Salvemini D, et al. A fluorometric assay for the measurement of nitrite in biological samples. Anal Biochem 1993;214(1):11–16.

    Article  PubMed  CAS  Google Scholar 

  174. Tsikas D, Sandmann J, Rossa S, et al. Gas chromatographic-mass spectrometric detection of S-nitrosocysteine and S-nitrosoglutathione. Anal Biochem 1999;272:117–122.

    Article  PubMed  CAS  Google Scholar 

  175. Chait BT, Kent SB. Weighing naked proteins: practical, high-accuracy mass measurement of peptides and proteins. Science 1992;257(5078):1885–1894.

    Article  PubMed  CAS  Google Scholar 

  176. Michel T, Feron O. Nitric oxide synthases: which, where, how, and why? J Clin Invest 1997;100(9): 2146–2152.

    Article  PubMed  CAS  Google Scholar 

  177. Fulton D, Gratton JP, Sessa WC. Post-translational control of endothelial nitric oxide synthase: why isn’t calciun/calmodulin enough? J Pharmacol Exp Ther 2001;299(3):818–824.

    PubMed  CAS  Google Scholar 

  178. Mayer B, Werner ER. In search of a function for tetrahydrobiopterin in the biosynthesis of nitric oxide. Naunyn Schmiedebergs Arch Pharmacol 1995;351(5):453–463.

    Article  PubMed  CAS  Google Scholar 

  179. Werner-Felmayer G, Golderer G, Werner ER. Tetrahydrobiopterin biosynthesis, utilization and pharmacological effects. Curr Drug Metab 2002;3(2):159–173.

    Article  PubMed  CAS  Google Scholar 

  180. Fulton D, Gratton JP, McCabe TJ, et al. Regulation of endothelium-derived nitric oxide production by the protein kinase Akt. Nature 1999;399(6736):597–601.

    Article  PubMed  CAS  Google Scholar 

  181. Ishida Y, Hashimoto M, Fukushima S, et al. A nitric oxide-sensitive electrode: requirement of lower oxygen concentration for detecting nitric oxide from the tissue. J Pharmacol Toxicol Methods 1996;35(1):19–24.

    Article  PubMed  CAS  Google Scholar 

  182. Ayajiki K, Kindermann M, Hecker M, et al. Intracellular pH and tyrosine phosphorylation but not calcium determine shear stress-induced nitric oxide production in native endothelial cells. Circ Res 1996;78(5):750–758.

    Article  PubMed  CAS  Google Scholar 

  183. Griscavage JM, Fukuto JM, Komori Y, et al. Nitric oxide inhibits neuronal nitric oxide synthase by interacting with the heme prosthetic group: role of tetrahydrobiopterin in modulating the inhibitory action of nitric oxide. J Biol Chem 1994;(269):21,644–21,649.

    CAS  Google Scholar 

  184. Du XL, Edelstein D, Dimmeler S, et al. Hyperglycemia inhibits endothelial nitric oxide synthase activity by posttranslational modification at the Akt site. J Clin Invest 2001;108(9):1341–1348.

    PubMed  CAS  Google Scholar 

  185. Flavahan NA, Vanhoutte PM. Endothelial cell signaling and endothelial dysfunction. Am J Hypertens 1995;8(5 pt 2):28S-41S.

    Article  PubMed  CAS  Google Scholar 

  186. Lin S, Fagan KA, Li KX, et al. Sustained endothelial nitric-oxide synthase activation requires capacitative Ca2+ entry. J Biol Chem 2000;275(24):17,979–17,985.

    Article  CAS  Google Scholar 

  187. Abrahamsson T, Brandt U, Marklund SL, et al. Vascular bound recombinant extracellular superoxide dismutase type C protects against the detrimental effects of superoxide radicals on endotheliumdependent arterial relaxation. Circ Res 1992;70(2):264–271.

    Article  PubMed  CAS  Google Scholar 

  188. Woodman CR, Muller JM, Rush JW, et al. Flow regulation of ecNOS and Cu/Zn SOD mRNA expression in porcine coronary arterioles. Am J Physiol 1999;276(3 pt 2):H1058-H1063.

    PubMed  CAS  Google Scholar 

  189. Beny JL, der Weid PY. Hydrogen peroxide: an endogenous smooth muscle cell hyperpolarizing factor. Biochem Biophys Res Commun 1991;176(1):378–384.

    Article  PubMed  CAS  Google Scholar 

  190. Iida Y, Katusic ZS. Mechanisms of cerebral arterial relaxations to hydrogen peroxide. Stroke 2000;31(9):2224–2230.

    Article  PubMed  CAS  Google Scholar 

  191. Matoba T, Shimokawa H, Nakashima M, et al. Hydrogen peroxide is an endothelium-derived hyperpolarizing factor in mice. J Clin Invest 2000;106(12):1521–1530.

    Article  PubMed  CAS  Google Scholar 

  192. Miura H, Bosnjak JJ, Ning G, et al. Role for hydrogen peroxide in flow-induced dilation of human coronary arterioles. Circ Res 2003;92(2):E31-E40.

    Article  PubMed  CAS  Google Scholar 

  193. Rand MJ, Li CG. Nitric oxide as a neurotransmitter in peripheral nerves: nature of transmitter and mechanism of transmission. Annu Rev Physiol 1995;57:659–682.

    Article  PubMed  CAS  Google Scholar 

  194. Luo D, Vincent SR. NMDA-dependent nitric oxide release in the hippocampus in vivo: interactions with noradrenaline. Neuropharmacology 1994;33(11):1345–1350.

    Article  PubMed  CAS  Google Scholar 

  195. Loesch A, Burnstock G. Ultrastructural localization of nitric oxide synthase and endothelin in coronary and oulmonarv arteries of newborn rats. Cell Tissue Res 1995:279(3):475–483.

    Article  PubMed  CAS  Google Scholar 

  196. Boulanger CM, Heymes C, Benessiano J, et al. Neuronal nitric oxide synthase is expressed in rat vascular smooth muscle cells: activation by angiotensin II in hypertension. Circ Res 1998;83(12): 1271–1278.

    Article  PubMed  CAS  Google Scholar 

  197. De Luca A, Li CG, Rand MJ, et al. Effects of omega-conotoxin GVIA on autonomic neuroeffector transmission in various tissues. Br J Pharmacol 1990;101(2):437–447.

    Article  PubMed  Google Scholar 

  198. Zygmunt PM, Zygmunt PK, Hogestatt ED, et al. Effects of omega-conotoxin on adrenergic, cholinergic and NANC neurotransmission in the rabbit urethra and detrusor. Br J Pharmacol 1993;110(4): 1285–1290.

    Article  PubMed  CAS  Google Scholar 

  199. Olgart C, Gustafsson LE, Wiklund NP. Evidence for nonvesicular nitric oxide release evoked by nerve activation. Eur J Neurosci 2000;12(4):1303–1309.

    Article  PubMed  CAS  Google Scholar 

  200. Kasakov L, Cellek S, Moncada S. Characterization of nitrergic neurotransmission during short and long-term electrical stimulation of the rabbit anococcygeus muscle. Br J Pharmacol 1995;115(7): 1149–1154.

    Article  PubMed  CAS  Google Scholar 

  201. Costa M, Furness JB, Pompolo S, et al. Projections and chemical coding of neurons with immunoreactivity for nitric oxide synthase in the guinea-pig small intestine. Neurosci Lett 1992;148(1–2): 121–125.

    Article  PubMed  CAS  Google Scholar 

  202. Murthy KS, Grider JR, Jin JG, et al. Interplay of VIP and nitric oxide in the regulation of neuromuscular activity in the gut. Arch Int Pharmacodyn Ther 1995;329(1):27–38.

    PubMed  CAS  Google Scholar 

  203. Bishop-Bailey D, Larkin SW, Warner TD, et al. Characterization of the induction of nitric oxide synthase and cyclo-oxygenase in rat aorta in organ culture. Br J Pharmacol 1997;121(1).125–133.

    Article  PubMed  CAS  Google Scholar 

  204. Chartrain NA, Geller DA, Koty PP, et al. Molecular cloning, structure, and chromosomal localization of the human inducible nitric oxide svnthase gene T Biol Chem 1994;769(9)6765–6772

    Google Scholar 

  205. Vazquez-Torres A, Jones-Carson J, Mastroeni P, et al. Antimicrobial actions of the NADPH phagocyte oxidase and inducible nitric oxide synthase in experimental salmonellosis. I. Effects on microbial killing by activated peritoneal macrophages in vitro. J Exp Med 2000;192(2):227–236.

    Article  PubMed  CAS  Google Scholar 

  206. Furchgott RF, Carvalho MH, Khan MT, et al. Evidence for endothelium-dependent vasodilation of resistance vessels by acetylcholine. Blood Vessels 1987;24(3):145–149.

    PubMed  CAS  Google Scholar 

  207. Duncan C, Dougall H, Johnston P, et al. Chemical generation of nitric oxide in the mouth from the enterosalivary circulation of dietary nitrate. Nat Med 1995;1(6):546–551.

    Article  PubMed  CAS  Google Scholar 

  208. Benjamin N. O’Driscoll F. Dougall H. et al. Stomach NO synthesis. Nature 1994:368(6471):502.

    Article  PubMed  CAS  Google Scholar 

  209. Weitzberg E, Lundberg JO. Nonenzymatic nitric oxide production in humans. Nitric Oxide 1998;2(1): 1–7.

    Article  PubMed  CAS  Google Scholar 

  210. Zweier JL, Samouilov A, Kuppusamy P. Non-enzymatic nitric oxide synthesis in biological systems. Biochim Biophys Acta 1999:1411(2–3):250–262.

    PubMed  CAS  Google Scholar 

  211. Zhang Z, Naughton D, Winyard PG, et al. Generation of nitric oxide by a nitrite reductase activity of xanthine oxidase: a potential pathway for nitric oxide formation in the absence of nitric oxide synthase activity. Biochem Biophys Res Commun 1998;249(3):767–772.

    Article  PubMed  CAS  Google Scholar 

  212. Lovren F, Triggle CR. Involvement of nitrosothiols, nitric oxide and voltage-gated K+ channels in photorelaxation of vascular smooth muscle. Eur J Pharmacol 1998;347(2–3):215–221.

    Article  PubMed  CAS  Google Scholar 

  213. Megson IL, Holmes SA, Magid KS, et al. Selective modifiers of glutathione biosynthesis and “repriming” of vascular smooth muscle photorelaxation. Br J Pharmacol 2000;130(7):1575–1580.

    Article  PubMed  CAS  Google Scholar 

  214. Matsunaga K, Furchgott RF. Interactions of light and sodium nitrite in producing relaxation of rabbit aorta. J Pharmacol Exp Ther 1989;248(2):687–695.

    PubMed  CAS  Google Scholar 

  215. Andrews KL, McGuire JJ, Triggle CR. A photosensitive vascular smooth muscle store of nitric oxide in mouse aorta: no dependence on expression of endothelial nitric oxide synthase. Br J Pharmacol 2003;138(5):932–940.

    Article  PubMed  CAS  Google Scholar 

  216. Denninger JW, Marletta MA. Guanylate cyclase and the NO/cGMP signaling pathway. Biochim Biophys Acta 1999;1411(2–3):334–350.

    PubMed  CAS  Google Scholar 

  217. Wedel B, Harteneck C, Foerster J, et al. Functional domains of soluble guanylyl cyclase. J Biol Chem 1995;270(42):24,871–24,875.

    CAS  Google Scholar 

  218. Robertson BE, Schubert R, Hescheler J, et al. cGMP-dependent protein kinase activates Ca-activated K channels in cerebral artery smooth muscle cells. Am J Physiol 1993;265(1 pt 1):C299-C303.

    PubMed  CAS  Google Scholar 

  219. Archer SL, Huang JM, Hampl V, et al. Nitric oxide and cGMP cause vasorelaxation by activation ot a charybdotoxin-sensitive K channel by cGMP-dependent protein kinase. Proc Natl Acad Sci USA 1994;91(16):7583–7587.

    Article  PubMed  CAS  Google Scholar 

  220. Bolotina VM, Najibi S, Palacino JJ, et al. Nitric oxide directly activates calcium-dependent potassium channels in vascular smooth muscle. Nature 1994;368:850–853.

    Article  PubMed  CAS  Google Scholar 

  221. Mistry DK, Garland CJ. Nitric oxide (NO)-induced activation of large conductance Ca2+-dependent K+ channels (BK(Ca)) in smooth muscle cells isolated from the rat mesenteric artery. Br J Pharmacol 1998;124(6):1131–1140.

    Article  PubMed  CAS  Google Scholar 

  222. Lang RJ, Harvey JR, McPhee GJ, et al. Nitric oxide and thiol reagent modulation of La2---activated iK+(BKKCa) channels in myocytes of the guinea-pig taenia caeci. J Physiol 2000;525(pt 2):363–376.

    Article  PubMed  CAS  Google Scholar 

  223. Haburcak M, Wei L, Viana F, et al. Calcium-activated potassium channels in cultured human endothelial cells are not directly modulated by nitric oxide. Cell Calcium 1997;21(4):291–300.

    Article  PubMed  CAS  Google Scholar 

  224. Jeong SY, Ha TS, Park CS, et al. Nitric oxide directly activates large conductance Ca2+-activated K+ channels (rSlo). Mol Cells 2001;12(1):97–102.

    PubMed  CAS  Google Scholar 

  225. Verma S, Lovren F, Dumont AS, et al. Tetrahydrobiopterin improves endothelial function in human sanhenous veins. J Thorac Cardiovasc sure 2000;120:668–671.

    Article  CAS  Google Scholar 

  226. Pannirselvam M, Verma S, Anderson JJ, and Triggle CR. Cellular basis of endothelial dysfunction in small mesenteric arteries from spontaneously diabetic (db/db-/-) mice: role of decreased tetrahydrobiopterin bioavailaility. Br J Pharmacol 2002;136(2):255–263.

    Article  PubMed  CAS  Google Scholar 

  227. Feletou M, Vanhoutte PM. Activation of vascular smooth muscle K-+ channels by endotheilum-derived factors. In: Archer SL, Rusch NJ, eds. Potassium Channels in Cardiovascular Biology. Kluwer Academic/Plenum: New York, 2001, pp. 691–723.

    Chapter  Google Scholar 

  228. McGuire JJ, Ding H, Triggle CR. Endothelium-derived relaxing factors: a focus on endotheliumderived hyperpolarizing factor(s). Can J Physiol Pharmacol 2001;79:443–470.

    Google Scholar 

  229. Busse R, Edwards G, Feletou M, et al. EDHF: bringing the concepts together. Trends Pharmacol Sci 2002;23(8):374–380

    Article  PubMed  CAS  Google Scholar 

  230. Triggle CR, Ding H. Endothelium-derived hyperpolarizing factor: is there a novel chemical mediator? Clin Exp Pharmacol Physiol 2002;29(3):153–160.

    Article  PubMed  CAS  Google Scholar 

  231. Ding H, Triggle CR. Relaxing blood vessels: are there novel endothelium-derived mediators to be found and can their discovery lead to the development of new therapeutic agents? Pharm News 2001:8(42):42–49.

    CAS  Google Scholar 

  232. Waldron GJ, Garland CJ. Contribution of both nitric oxide and a change in membrane potential to acetylcholine-induced relaxation in the rat small mesenteric artery. Br J Pharmacol 1994;112(3): 831–836

    Article  PubMed  CAS  Google Scholar 

  233. Edwards G, Dora KA, Gardener MJ, et al. K+ is an endothelium-derived hyperpolarizing factor in rat arteries. Nature 1998;396(6708):269–272.

    Article  PubMed  CAS  Google Scholar 

  234. Ding H, Triggle CR. The contribution of EDHF and role of postassium channels inhibitors in of vascular tone. Drug Discovery Res 2003;58:81–89.

    CAS  Google Scholar 

  235. Hinton JM, Langton PD. Inhibition of LUMF by two new combinations or K(+)-channel inhibitors in rat isolated mesenteric arteries. Br J Pharmacol 2003;138(6):1031–1035.

    Article  PubMed  CAS  Google Scholar 

  236. Dong H, Jiang Y, Cole WC, et al. Comparison of the pharmacological properties of EDHF-mediated vasorelaxation in guinea-pig cerebral and mesenteric resistance vessels. Br J Pharmacol 2000;130(8): 1983–1991.

    Article  PubMed  CAS  Google Scholar 

  237. Fisslthaler B, Popp R, Kiss L, et al. Cytochrome P450 2C is an EDHF synthase in coronary arteries. Nature 1999;401(6752):493–497.

    Article  PubMed  CAS  Google Scholar 

  238. Sandow SL, Hill CE. Incidence of myoendothelial gap junctions in the proximal and distal mesenteric arteries of the rat is suggestive of a role in endothelium-derived hyperpolarizing factor-mediated responses. Circ Res 2000:86(3):341–346.

    Article  PubMed  CAS  Google Scholar 

  239. Coleman HA, Tare M, Parkington HC. K+ currents underlying the action of endothelium-derived hyperpolarizing factor in guinea-pig, rat and human blood vessels. J Physiol 2001;531(pt 2):359–373.

    Article  PubMed  CAS  Google Scholar 

  240. Chaytor AT, Evans WH, Griffith TM. Central role of heterocellular gap junctional communication in endothelium-dependent relaxations of rabbit arteries. J Physiol 1998;508 (pt 2):561–573.

    Article  PubMed  CAS  Google Scholar 

  241. Dora KA, Martin PE, Chaytor AT, et al. Role of heterocellular Gap junctional communication in endothelium-dependent smooth muscle hyperpolarization: inhibition by a connexin-mimetic peptide. Biochem Biophys Res Commun 1999;254(1):27–31.

    Article  PubMed  CAS  Google Scholar 

  242. Edwards G, Weston AH. EDHF-are there gaps in the pathway? J Physiol 2001;531(pt 2):299.

    Article  PubMed  CAS  Google Scholar 

  243. Ujiie H, Chaytor AT, Bakker LM, et al. Essential role of Gap junctions in NO- and prostanoid-independent relaxations evoked by acetylcholine in rabbit intracerebral arteries. Stroke 2003;34(2):544–550.

    Article  PubMed  CAS  Google Scholar 

  244. Emerson GG, Segal SS Electrical coupling oetween enaotneliai cens ana smootn muscle cells in hamster feed arteries: role in vasomotor control. Circ Res 2000;87(6):474–479.

    Article  PubMed  CAS  Google Scholar 

  245. Emerson GG, Segal SS. Endothelial cell pathway for conduction of hyperpolarization and vasodilation along hamster feed artery. Circ Res 2000;86(1):94–100.

    Article  PubMed  CAS  Google Scholar 

  246. Welsh DG, Segal SS. Role of EDHF in conduction of vasodilation along hamster cheek pouch arterioles in vivo. Am J Physiol Heart Circ Physiol 2000;278(6):H1832-H1839.

    PubMed  CAS  Google Scholar 

  247. Matoba T, Shimokawa H, Kubota H, et al. Hydrogen peroxide is an endothelium-derived hyperpolarizing factor in human mesenteric arteries. Biochem Biophys Res Commun 2002;290(3):909–913.

    Article  PubMed  CAS  Google Scholar 

  248. Matoba T, Shimokawa H, Morikawa K, et al. Electron spin resonance detection of hydrogen peroxide as an endothelium-derived hyperpolaiizing factor in porcine coronary microvessels. Arterioscl Thromb Vasc Biol 2003;23(7):1224–1230.

    Article  PubMed  CAS  Google Scholar 

  249. Matoba T, Shimokawa H. Hydrogen peroxide is an endothelium-derived hyperpolarizing factor in animals and humans. J Pharmacol Sci 2003:92(1):1–6.

    Article  PubMed  CAS  Google Scholar 

  250. Cohen RA, Plane F, Najibi S, et al. Nitric oxide is the mediator of both endothelium-dependent relaxation and hyperpolarization of the rabbit carotid artery. Proc Natl Acad Sci USA 1997;94(8):4193–4198.

    Article  PubMed  CAS  Google Scholar 

  251. Bauersachs J, Popp R, Hecker M, et al. Nitric oxide attenuates the release of endothelium-derived hyperpolarizing factor. Circulation 1996;94(12):3341–3347.

    Article  PubMed  CAS  Google Scholar 

  252. Deshpande NN, Sorescu D, Seshiah P, et al. Mechanism of hydrogen peroxide-induced cell cycle arrest in vascular smooth muscle. Antioxid Redox Signal 2002;4(5):845–854.

    Article  PubMed  CAS  Google Scholar 

  253. Rabelo LA, Cortez SF, Alvarez-Leite JI, et al. Endothelium dysfunction in LDL receptor knockout mice: a role for H2O2. Br J Pharmacol 2003;138(5):1215–1220.

    Article  PubMed  CAS  Google Scholar 

  254. Pomposiello S, Rhaleb NE, Alva M, et al. Reactive oxygen species: role in the relaxation induced by bradykinin or arachidonic acid via EDHF in isolated porcine coronary arteries. J Cardiovasc Pharmacol 1999;34(4):567–574.

    Article  PubMed  CAS  Google Scholar 

  255. Hamilton CA, McPhaden AR, Berg G, et al. Is hydrogen peroxide an EDHF in human radial arteries? Am J Physiol Heart Circ Physiol 2001:280(6):H2451-H2455.

    PubMed  CAS  Google Scholar 

  256. Ellis A, Pannirselvam M, Anderson TJ, et al. Catalase has negligible inhibitory effects on endotheliumdependent relaxation in mouse isolated aorta and small mesenteric artery. Br J Pharmacol 2003;140(7): 1193–1200

    Article  PubMed  CAS  Google Scholar 

  257. Ellis A, Triggle CR. Endothelium-derived reactive oxygen species: their relationship to endotheliumdependent hyperpolarization and the regulation of vascular tone. Can J. Physiol Pharmacol. 2003;81(11):1013–1028.

    Article  PubMed  CAS  Google Scholar 

  258. McCarron JG, Halpern W. Potassium dilates rat cerebral arteries by two independent mechanisms. Am J Physiol 1990;259(3 pt 2):H902-H908.

    PubMed  CAS  Google Scholar 

  259. Knot HJ, Zimmermann PA, Nelson MT. Extracellular K(+)-induced hyperpolarizations and dilatations of rat coronary and cerebral arteries involve inward rectifier K(+) channels. J Physiol 1996; 492(pt 2):419–430.

    PubMed  CAS  Google Scholar 

  260. Taddei S, Mattei P, Virdis A, et al. Effect of potassium on vasodilation to acetylcholine in essential hypertension. Hypertension 1994;23(4):485–490.

    Article  PubMed  CAS  Google Scholar 

  261. Pannirselvam M, Anderson TJ, Triggle CR. Endothelial cell dysfunction in type I and II diabetes-the cellular basis for dysfunction. Drug Discovery Res 2003;58:28–41.

    CAS  Google Scholar 

  262. Angulo J, Cuevas P, Fernandez A, et al. Calcium dobesilate potentiates endothelium-derived hyperpolarizing factor-mediated relaxation of human penile resistance arteries. Br J Pharmacol 2003;139(4):854–862.

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. Chris R. Triggle
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  2. Hong Ding
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  3. Ella S. M. Ng
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  4. Anthie Ellis
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Editor information

Editors and Affiliations

  1. Department of Physiology, University of Saskatchewan, Saskatoon, SK, Canada

    Rui Wang MD, PhD, FAHA

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Triggle, C.R., Ding, H., Ng, E.S.M., Ellis, A. (2004). Nitric Oxide. In: Wang, R. (eds) Signal Transduction and the Gasotransmitters. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-806-9_3

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  • DOI: https://doi.org/10.1007/978-1-59259-806-9_3

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-512-5

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