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New Regulatory, Signaling Pathways, and Sources of Nitric Oxide

  • Takumi Sozen
  • Reiko Tsuchiyama
  • Yu Hasegawa
  • Hidenori Suzuki
  • Vikram Jadhav
  • Shigeru Nishizawa
  • John H. Zhang
Conference paper
Part of the Acta Neurochirurgica Supplements book series (NEUROCHIRURGICA, volume 110/1)

Abstract

Discovered in 1980 by the late Robert F. Furchgott, endothelium-derived relaxing factor, nitric oxide (NO), has been in the forefront of vascular research for several decades. What was originally a narrow approach, has been significantly widened due to major advances in understanding the chemical and biological properties of NO as well as its signaling pathways and discovering new sources of this notorious free radical gas. In this review, recent discoveries regarding NO and their implications on therapy for delayed cerebral vasospasm are presented.

Keywords

Hemoglobin Neuroglobin Nitric oxide SAH Vasospasm 

Notes

Acknowledgment

This research was supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke at the NIH.

Conflict of interest statement

The author is one of holders of the international patent on sodium nitrite use in cerebrovascular diseases.

References

  1. 1.
    Ignarro L. Nitric oxide as a unique signaling molecule in the vascular system: a historical overview. J Physiol Pharmacol. 2002;53:503–14.PubMedGoogle Scholar
  2. 2.
    Gladwin M, Crawford J, Patel R. The biochemistry of nitric oxide, nitrite, and hemoglobin: role in blood flow regulation. Free Rad Biol Med. 2004;36:707–16.PubMedCrossRefGoogle Scholar
  3. 3.
    Liu X, Miller MJS, Joshi MS, Sadowska-Krowicka H, Clark DD, Lancaster Jr JR. Diffusion-limited reaction of free nitric oxide with erythrocytes. J Biol Chem. 1998;273:18709–13.PubMedCrossRefGoogle Scholar
  4. 4.
    Khurana VG, Sohni YR, Mangrum WI, McClelland RL, O’Kane DJ, Meyer FB, et al. Endothelial nitric oxide synthase gene polymorphism predict susceptibility to aneurismal subarachnoid hemorrhage and cerebral vasospasm. J Cereb Blood Flow Metabol. 2004;24:291–7.Google Scholar
  5. 5.
    Kukreja RC, Xi L. eNOS phosphorylation: a pivotal molecular switch in vasodilation and cardioprotection? J Mol Cell Cardiol. 2007;42(2):280–2.PubMedCrossRefGoogle Scholar
  6. 6.
    Vallance P, Leone A, Calver A, Collier J, Moncada S. Endogenous dimethylarginine as an inhibitor of nitric oxide synthesis. J Cardiovasc Pharmacol. 1992;20(Suppl 12):S60–2.PubMedCrossRefGoogle Scholar
  7. 7.
    Jung CS, Oldfield EH, Harvey-White J, Espey MG, Zimmermann M, Seifert V, et al. Association of an endogenous inhibitor of nitric oxide synthase with cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage. J Neurosurg. 2007;107(5):945–50.PubMedCrossRefGoogle Scholar
  8. 8.
    Pluta RM, Jung CS, Judith Harvey-White J, Whitehead A, Espey MG, et al. In vitro and in vivo effects of probucol on hydrolysis of asymmetric dimethyl l-arginine and vasospasm in primates. J Neurosurg. 2005;103:731–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Morris SM Jr. Recent advances in arginine metabolism: roles and regulation of the arginases. Br J Pharmacol. 2009;157(6):922–30.PubMedCrossRefGoogle Scholar
  10. 10.
    Stuehr S, Pou S, Rosen G. Oxygen reduction by nitric oxide synthases. J Biol Chem. 2001;276:14533–6.PubMedCrossRefGoogle Scholar
  11. 11.
    Cai H. Hydrogen peroxide regulation of endothelial function: origins, mechanisms, and consequences. Cardiovasc Res. 2005;68(1):26–36.PubMedCrossRefGoogle Scholar
  12. 12.
    Pluta RM, Afshar JK, Thompson BG, Boock RJ, Harvey-White J, Oldfield EH. Increased cerebral blood flow but no reversal or prevention of vasospasm in response to L-arginine infusion after subarachnoid hemorrhage. J Neurosurg. 2000;92:121–6.PubMedCrossRefGoogle Scholar
  13. 13.
    Pluta R. Delayed cerebral vasospasm and nitric oxide: review, new hypothesis, and proposed treatment. Pharmacol Ther. 2005;105:23–56.PubMedCrossRefGoogle Scholar
  14. 14.
    Desai A, Zhao Y, Heather A, Lankford HA, Warren JS. Nitric oxide suppresses EPO-induced monocyte chemoattractant protein-1 in endothelial cells: implications for atherogenesis in chronic renal disease. Lab Invest. 2006;86(4):369–79.PubMedCrossRefGoogle Scholar
  15. 15.
    Sirén AL, Fratelli M, Brines M, Goemans C, Casagrande S, Lewczuk P, et al. Erythropoietin prevents neuronal apoptosis after cerebral ischemia and metabolic stress. Proc Natl Acad Sci USA. 2001;98(7):4044–9.PubMedCrossRefGoogle Scholar
  16. 16.
    Banerjee D, Rodriguez M, Nag M, Adamson JW. Exposure of endothelial cells to recombinant human erythropoietin induces nitric oxide synthase activity. Kidney Int. 2000;57(5):1895–904.PubMedCrossRefGoogle Scholar
  17. 17.
    Isenberg JS, Shiva S, Gladwin M. Thrombospondin-1-CD47 blockade and exogenous nitrite enhance ischemic tissue survival, blood flow and angiogenesis via coupled NO-cGMP pathway activation. Nitric Oxide. 2009;21(1):52–62.PubMedCrossRefGoogle Scholar
  18. 18.
    Sobey C. Cerebrovascular dysfunction after subarachnoid hemorrhage: novel mechanisms and directions for therapy. Clin Exp Pharm Physiol. 2001;28:926–9.CrossRefGoogle Scholar
  19. 19.
    Kim P, Schini VB, Sundt Jr TM, Vanhoutte PM. Reduced production of cGMP underlies the loss of endothelium-dependent relaxations in the canine basilar artery after subarachnoid hemorrhage. Circ Res. 1992;70:248–56.PubMedCrossRefGoogle Scholar
  20. 20.
    Edwards D, Byrne J, Griffith T. The effect of chronic subarachnoid hemorrhage on basal endothelium-derived relaxing factor activity in intrathecal cerebral arteries. J Neurosurg. 1992;76:830–7.PubMedCrossRefGoogle Scholar
  21. 21.
    Kasuya H, Weir BK, Nakane M, Pollock JS, Johns L, Marton LS, et al. Nitric oxide synthase and guanylate cyclase levels in canine basilar artery after subarachnoid hemorrhage. J Neurosurg. 1995;82:250–5.Google Scholar
  22. 22.
    Yamaguchi-Okada M, Nishizawa S, Mizutani A, Namba H. Multifaceted effects of selective inhibitor of phosphodiesterase III, cilostazol, for cerebral vasospasm after subarachnoid hemorrhage in a dog model. Cerebrovasc Dis. 2009;28(2):135–42.PubMedCrossRefGoogle Scholar
  23. 23.
    Willette RN, Shiloh AO, Sauermelch CF, Sulpizio A, Michell MP, Cieslinski LB, et al. Identification, characterization, and functional role of phosphodiesterase type IV in cerebral vessels: effects of selective phosphodiesterase inhibitors. J Cereb Blood Flow Metab. 1997;17(2):210–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Malinski T, Bailey F, Zhang ZG, Chopp M. Nitric oxide measured by a porphyrinic microsensor in rat brain after transient middle cerebral artery occlusion. J Cereb Blood Flow Metabol. 1993;13:355–8.CrossRefGoogle Scholar
  25. 25.
    Doyle M, Hoekstra J. Oxidation of nitrogen oxides by bound dioxygen in hemoproteins. J Inorg Biochem. 1981;14:351–8.PubMedCrossRefGoogle Scholar
  26. 26.
    Pluta RM, Dejam A, Grimes G, Gladwin MT, Oldfield EH. Nitrite infusions prevent cerebral artery vasospasm in a primate model of subarachnoid aneurismal hemorrhage. JAMA 2005;293:1477–84.PubMedCrossRefGoogle Scholar
  27. 27.
    Gladwin MT, Kim-Shapiro DB. The functional nitrite reductase activity of the heme-globins. Blood 2008;112(7):2636–47.PubMedCrossRefGoogle Scholar
  28. 28.
    Ignarro L. Biosynthesis and metabolism of endothelium-derived nitric oxide. Annu Rev Pharmacol Toxicol. 1990;30:535–60.PubMedCrossRefGoogle Scholar
  29. 29.
    Gladwin MT, Shelhamer JH, Schechter AN, Pease-Fye ME, Waclawiw MA, Panza JA, et al. Role of circulating nitrite and S-nitrosohemoglobin in the regulation of regional blood flow in humans. Proc Natl Acad Sci USA. 2000;97:11482–7.PubMedCrossRefGoogle Scholar
  30. 30.
    Cosby K, Partovi KS, Crawford JH, Patel RP, Reiter CD, Martyr S, et al. Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation. Nat Med. 2003;9:1498–505.PubMedCrossRefGoogle Scholar
  31. 31.
    Dejam A, Hunter CJ, Schechter AN, Gladwin MT. Emerging role of nitrite in human biology. Blood Cell Mol Dis. 2004;32:423–9.CrossRefGoogle Scholar
  32. 32.
    Afshar JK, Pluta RM, Boock RJ, Thompson BG, Oldfield EH. Effect of intracarotid nitric oxide on primate cerebral vasospasm after subarachnoid hemorrhage. J Neurosurg. 1995;83:118–22.PubMedCrossRefGoogle Scholar
  33. 33.
    Pluta R, Oldfield E, Boock R. Reversal and prevention of cerebral vasospasm by intracarotid infusions of nitric oxide donors in a primate model of subarachnoid hemorrhage. J Neurosurg. 1997;87:746–51.PubMedCrossRefGoogle Scholar
  34. 34.
    Pluta RM, Afshar JK, Boock RJ, Oldfield EH. Temporal changes in perivascular concentrations of oxyhemoglobin, deoxyhemoglobin and, methemoglobin in subarachnoid hemorrhage. J Neurosurg. 1998;88:557–61.PubMedCrossRefGoogle Scholar
  35. 35.
    Hashi K, Meyer JS, Shinmaru S, Welch KM, Teraura T. Cerebral hemodynamic and metabolic changes after subarachnoid hemorrhage. J Neurol Sci. 1972;17:1–14.PubMedCrossRefGoogle Scholar
  36. 36.
    Khaldi A, Zauner A, Reinert M, Woodward JJ, Bullock MR. Measurements of nitric oxide and brain tissue oxygen tension in patients after severe subarachnoid hemorrhage. Neurosurgery 2001;49:33–40.PubMedGoogle Scholar
  37. 37.
    Webb AJ, Patel N, Loukogeorgakis S, Okorie M, Aboud Z, Misra S, et al. Acute blood pressure lowering, vasoprotective, and antiplatelet properties of dietary nitrate via bioconversion to nitrite. Hypertension 2008;51(3):784–90.PubMedCrossRefGoogle Scholar
  38. 38.
    Lundberg JO, Weitzberg E. NO generation from inorganic nitrate and nitrite: role in physiology, nutrition and therapeutics. Arch Pharm Res. 2009;32(8):1119–26.PubMedCrossRefGoogle Scholar
  39. 39.
    Jansson EA, Huang L, Malkey R, Govoni M, Nihlén C, Olsson A, et al. A mammalian functional nitrate reductase that regulates nitrite and nitric oxide homeostasis. Nat Chem Biol. 2008;4(7):411–7.PubMedCrossRefGoogle Scholar
  40. 40.
    Burmester T, Hankeln T. Neuroglobin: a respiratory protein of the nervous system. News Physiol Sci. 2004;19:110–3.PubMedGoogle Scholar
  41. 41.
    Petersen MG, Dewilde S, Fago A. Reactions of ferrous neuroglobin and cytoglobin with nitrite under anaerobic conditions. J Inorg Biochem. 2008;102(9):1777–82.PubMedCrossRefGoogle Scholar
  42. 42.
    Bryan NS, Rassaf T, Maloney RE, Rodriguez CM, Fumito Saijo, Juan R. Rodriguez, et al. Cellular targets and mechanism of nitros(yl)ation: an insight into their nature and kinetics in vivo. PNAS. 2004;101:4308–13.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag/Wien 2011

Authors and Affiliations

  • Takumi Sozen
    • 1
    • 2
  • Reiko Tsuchiyama
    • 3
  • Yu Hasegawa
    • 3
  • Hidenori Suzuki
    • 3
  • Vikram Jadhav
    • 3
  • Shigeru Nishizawa
    • 2
  • John H. Zhang
    • 3
    • 4
  1. 1.Department of NeurosurgeryUniversity of Occupational and Environmental HealthKitakyushuJapan
  2. 2.Department of NeurosurgeryUniversity of Occupational and Environmental HealthJapan
  3. 3.Department of PhysiologyLoma Linda University of MedicineLoma LindaUSA
  4. 4.Department of NeurosurgeryLoma Linda University of MedicineLoma LindaUSA

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