Skip to main content
SpringerLink
Log in

The Role of Nitric Oxide in Hemorrhagic Shock and Trauma

  • Conference paper
Shock, Sepsis, and Organ Failure — Nitric Oxide

Abstract

The systemic response to hemorrhagic shock and trauma has the overall objective of restoring body homeostasis. This response involves a complex array of organ interactions, and in patients with severe injuries it is essential for survival. Under certain circumstances, however, the response itself may be deleterious and can result in further tissue injury and death [1]. Governing this response is a series of mediators, including endocrine, neural, and immune components such as catecholamines, Cortisol, multiple cytokines, complement, and products of arachidonic acid metabolism. Studies which differentiate the roles played by individual mediators continue to be central to our current understanding of the injured patient.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Gann DS, Foster AH (1993) Endocrine and metabolic responses to injury. In: Schwartz SI, Shires GT, Spencer FC, Husser WC (eds) Principles of surgery, 6th edn. McGraw-Hill, New York

    Google Scholar 

  2. Moncada S, Palmer RMJ, Higgs EA (1989) Biosynthesis of nitric oxide from L-arginine. A pathway for the regulation of cell function and communication. Biochem Pharmacol 38: 1709–1715

    Google Scholar 

  3. Koshland DE Jr (1992) The molecule of the year. Science 258: 1861

    Article  PubMed  Google Scholar 

  4. Hibbs JB Jr, Taintor RR, Vavrin Z (1987) Macrophage cytotoxicity: role for L-arginine deiminase and imino nitrogen oxidation to nitrite. Science 235: 473–476

    Article  PubMed  CAS  Google Scholar 

  5. Stuehr DJ, Nathan CF (1989) Nitric oxide: a macrophage product responsible for cytostasis and respiratory inhibition in tumor target cells. J Exp Med 169: 1545–1555

    Google Scholar 

  6. Parks NJ, Krohn KA, Mathis CA, Chasko JH, Geiger KR, Gregor ME, PeekNF (1981) Nitrogen-13-labeled nitrite and nitrate: distribution and metabolism after intratracheal administration. Science 212: 58–61

    Article  PubMed  CAS  Google Scholar 

  7. Mitchell HH, Shonle HA, Grindley HS (1916) The origin of the nitrates in the urine. J Biol Chem 24: 461–490

    CAS  Google Scholar 

  8. Green LC, Ruiz de Luzuriaga K, Wagner DA, Rand W, Istfan N, Young VR, Tannen-baum SR (1981) Nitrate biosynthesis in man. Proc Natl Acad Sci USA 78: 7764–7768

    Google Scholar 

  9. Green LC, Tannenbaum SR, Goldman P (1981) Nitrate synthesis in the germfree and conventional rat. Science 212: 56–58

    Article  PubMed  CAS  Google Scholar 

  10. Wagner DA, Young VR, Tannenbaum SR (1983) Mammalian nitrate biosynthesis: incorporation of 15NH3 into nitrate is enhanced by endotoxin treatment. Proc Natl Acad Sci USA 80: 4518–4521

    Article  PubMed  CAS  Google Scholar 

  11. Stuehr DJ, Marietta MA (1987) Synthesis of nitrite and nitrate in murine macrophage cell lines. Cancer Res 47: 5590–5594

    PubMed  CAS  Google Scholar 

  12. Hibbs JB Jr, Taintor RR, Vavrin Z, Rachlin EM (1988) Nitric oxide: a cytotoxic activated macrophage effector molecule. Biochem Biophys Res Commun 157: 87–94

    Article  PubMed  CAS  Google Scholar 

  13. Furchgott RF, Zawadzki JV (1980) The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 228: 373–376

    Article  Google Scholar 

  14. Palmer RMJ, Rees DD, Ashton DS, Moncada S (1988) L-Arginine is the physiological pre-cursor for the formation of nitric oxide in endothelium-dependent relaxation. Biochem Biophys Res Commun 153: 1251–1256

    Article  PubMed  CAS  Google Scholar 

  15. Palmer RMJ, Ashton DS, Moncada S (1988) Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature 333: 664–666

    Article  PubMed  CAS  Google Scholar 

  16. 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  PubMed  CAS  Google Scholar 

  17. Martin GR, Bolofo ML, Giles H (1991) Inhibition of endothelium-dependent vasorelaxation by arginine analogues: a pharmacological analysis of agonist and tissue dependence. Br J Pharmacol 105: 643–652

    Google Scholar 

  18. Gruetter CA, Gruetter DY, Lyon JE, Kadowitz PJ, Ignarro LJ (1981) Relationship between cyclic guanosine 3-monophosphate formation and relaxation of coronary arterial smooth muscle by glyceryl trinitrate, nitroprusside, nitrite, and nitric oxide: effects of methylene blue and methemoglobin. J Pharmacol Exp Ther 219: 181–186

    PubMed  CAS  Google Scholar 

  19. XieQ-w, ChoHJ, CalaycayJ, MumfordRA, SwiderekKM, Lee TD, Ding A, Troso T, Nathan C (1992) Cloning and characterization of inducible nitric oxide synthase from mouse macrophages. Science 256: 225–228

    Google Scholar 

  20. Geller DA, Lowenstein CJ, Shapiro RA, Nussler AK, Di Silvio M, Wang SC, Nakayama DK, Simmons RL, Snyder SH, Billiar TR (1993) Molecular cloning and expression of inducible nitric oxide synthase from human hepatocytes. Proc Natl Acad Sci USA 90: 3491–3495

    Article  PubMed  CAS  Google Scholar 

  21. Bredt DS, Hwang PM, Glatt CE, Lowenstein C, Reed RR, Snyder SH (1991) Cloned and expressed nitric oxide synthase structurally resembles cytochrome P. 450 reductase. Nature 351: 714–718

    Article  PubMed  CAS  Google Scholar 

  22. Lamas S, Marsden PA, Li GK, Tempst P, Michel T (1992) Endothelial nitric oxide synthase: molecular cloning and characterization of a distinct constitutive enzyme isoform. Proc Natl Acad Sci USA 89: 6348–6352

    Article  PubMed  CAS  Google Scholar 

  23. Lyons CR, Orloff GJ, Cunningham JM (1992) Molecular cloning and functional expression of an inducible nitric oxide synthase from a murine macrophage cell line. J Biol Chem 267: 6370–6374

    PubMed  CAS  Google Scholar 

  24. Bredt DS, Glatt CE, Hwang PM, Fotuhi M, Dawson TM, Snyder SH (1991) Nitric oxide synthase protein and mRNA are discretely localized in neuronal populations of the mammalian CNS together with NADPH diaphorase. Neuron 7: 615–624

    Article  PubMed  CAS  Google Scholar 

  25. Nakane M, Schmidt HHHW, Pollock JS, Forstermann U, Murad F (1993) Cloned human brain nitric oxide synthase is highly expressed in skeletal muscle. FEBS Lett 316: 175–180

    Article  PubMed  CAS  Google Scholar 

  26. Nathan CF, Stuehr DJ (1990) Does endothelium-derived nitric oxide have a role in cytokine-induced hypotension? J Natl Cancer Inst 82: 726–728

    Article  PubMed  CAS  Google Scholar 

  27. Janssens SP, Shimouchi A, Quertermous T, Bloch DB, Block KD (1992) Cloning and expression of cDNA encoding human endothelium-derived relaxing factor/nitric oxide synthase. J Biol Chem 267: 14519–14522

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  29. OchoaJB, CurtiB, PeitzmanAB, Simmons RL, Billiar TR, Hoffman R, Rault R, Longo DL, Urba WJ, Ochoa AC (1992) Increased circulating nitrogen oxides after human tumor immunotherapy correlate with toxic hemodynamic changes. J Natl Cancer Inst 84: 864–867

    Google Scholar 

  30. FreeswickPD, WanY, Geller DA, NusslerAK, BilliarTR (1994) Remote tissue injury primes hepatocytes for nitric oxide synthesis. J Surg Res (in press)

    Google Scholar 

  31. BilliarTR, Curran RD, Harbrecht BG, Stadler J, Williams DL, OchoaJB, Di Silvio M, Simmons RL, Murray SA (1992) Association between synthesis and release of cGMP and nitric oxide biosynthesis by hepatocytes. Am J Physiol 262: C1077–C1082

    Google Scholar 

  32. Kilbourn RG, Gross SS, Jubran A, Adams J, Griffith OW, Levi R, Lodato RF (1990) NG-Methyl-L-arginine inhibits tumor necrosis factor-induced hypotension: implications for the involvement of nitric oxide. Proc Natl Acad Sci USA 87: 3629–3632

    Article  PubMed  CAS  Google Scholar 

  33. Rees DD, Palmer RMJ, Moncada S (1989) Role of endothelium-derived nitric oxide in the regulation of blood pressure. Proc Natl Acad Sci USA 86: 3375–3378

    Article  PubMed  CAS  Google Scholar 

  34. AisakaK, Gross SS, Griffith OW, LeviR (1989) NG-Methylarginine, an inhibitor of endothelium-derived nitric oxide synthesis, is a potent pressor agent in the guinea pig. Does nitric oxide regulate blood pressure in vivo? Biochem Biophys Res Commun 160: 881–886

    Google Scholar 

  35. Hibbs JB Jr, Westenfelder C, Taintor R, Vavrin Z, Kablitz C, Baranowski RL, Ward JH, Menlove RL, McMurry MP, Kushner JP, Samlowski WE (1992) Evidence for cytokine-inducible nitric oxide synthesis from L-arginine in patients receiving interleukin-2 therapy. J Clin Invest 89: 867–877

    Article  PubMed  Google Scholar 

  36. Petros A, Bennett D, Vallance P (1991) Effect of nitric oxide synthase inhibitors on hypotension in patients with septic shock. Lancet 338: 1557–1558

    Article  PubMed  CAS  Google Scholar 

  37. Stadler J, Curran RD, OchoaJB, Harbrecht BG, Hoffman RA, Simmons RL, BilliarTR (1991) Effect of endogenous nitric oxide on mitochondrial respiration of rat hepatocytes in vitro and in vivo. Arch Surg 126: 186–191

    Google Scholar 

  38. Stadler J, Biliar TR, Curran RD, Stuehr DJ, Ochoa JB, Simmons RL (1991) Effect of exogenous and endogenous nitric oxide on mitochondrial respiration of rat hepatocytes. Am J Physiol 260: C910–C916

    PubMed  CAS  Google Scholar 

  39. Ignarro LJ, Byrns RE, Buga GM, Wood KS, Chaudhuri G (1988) Pharmacological evidence that endothelium-derived relaxing factor is nitric oxide: use of pyrogallol and superoxide dismutase to study endothelium-dependent and nitric oxide-elicited vascular smooth muscle relaxation. J Pharmacol Exp Ther 244: 181–189

    PubMed  CAS  Google Scholar 

  40. Oda H, Kusumoto S, Nakajima T (1975) Nitrosyl-hemoglobin formation in the blood of animals exposed to nitric oxide. Arch Environ Health 30: 453–455

    PubMed  CAS  Google Scholar 

  41. Yoshida K, Kasama K (1987) Biotransformation of nitric oxide. Environ Health Perspect 73: 201–206

    Article  PubMed  CAS  Google Scholar 

  42. Denis M (1991) Tumor necrosis factor and granulocyte macrophage-colony stimulating factor stimulate human macrophages to restrict growth of virulent Mycobacterium avium and to kill avirulent M. avium: killing effector mechanism depends on the generation of reactive nitrogen intermediates. J Leukoc Biol 49: 380–387

    PubMed  CAS  Google Scholar 

  43. Miwa M, Stuehr DJ, Marietta MA, Wishnok JS, Tannenbaum SR (1987) Nitrosation of amines by stimulated macrophages. Carcinogenesis 8: 955–958

    Article  PubMed  CAS  Google Scholar 

  44. Murray HW, Teitelbaum RF (1992) L-Arginine-dependent reactive nitrogen intermediates and the antimicrobial effect of activated human mononuclear phagocytes. J Infect Dis 165: 513–517

    Article  PubMed  CAS  Google Scholar 

  45. Billiar TR, Curran RD, Stuehr DJ, Stadler J, Simmons RL, Murray SA (1990) Inducible cytosolic enzyme activity for the production of nitrogen oxides from L-arginine in hepatocytes. Biochem Biophys Res Commun 168: 1034–1040

    Article  PubMed  CAS  Google Scholar 

  46. Geller DA, Nussler AK, Di Silvio M, Lowenstein CJ, Shapiro RA, Wang SC, Simmons RL, Billiar TR (1993) Cytokines, endotoxin, and glucocorticoids regulate the expression of inducible nitric oxide synthase in hepatocytes. Proc Natl Acad Sci USA 90: 522–526

    Article  PubMed  CAS  Google Scholar 

  47. Finkel MS, Oddis CV, Jacob TD, Watkins SC, Hattler BG, Simmons RL (1992) Negative inotropic effects of cytokines on the heart mediated by nitric oxide. Science 257: 387–389

    Article  PubMed  CAS  Google Scholar 

  48. O’Connor KJ, Moncada S (1991) Glucocorticoids inhibit the induction of nitric oxide synthase and the related cell damage in adenocarcinoma cells. Biochim Biophys Acta 1097: 227–231

    PubMed  Google Scholar 

  49. Green SJ, Crawford RM, Hockmeyer JT, Meitzer MS, Nacy CA (1990) Leishmania major amastigotes initiate the L-arginine-dependent killing mechanism in IFN-γ-stimulated macrophages by induction of tumor necrosis factor-a. J Immunol 145: 4290–4297

    PubMed  CAS  Google Scholar 

  50. Li L, Kilbourn RG, Adams J, Fidler IJ (1991) Role of nitric oxide in lysis of tumor cells by cytokine-activated endothelial cells. Cancer Res 51: 2531–2535

    PubMed  CAS  Google Scholar 

  51. Nussler A, Drapier JC, Renia L et al (1991) L-Arginine-dependent destruction of intrahepatic malaria parasites in response to tumor necrosis factor and/or 1L-6 stimulation. Eur J Immunol 21: 227–230

    Article  PubMed  CAS  Google Scholar 

  52. Christou NV, McLean APH, Meakins JL (1980) Host defense in blunt trauma: interrelationships of kinetics of anergy and depressed neutrophil function, nutritional status, and sepsis. J Trauma 20: 833–841

    Article  PubMed  CAS  Google Scholar 

  53. OchoaJB, Udekwu AO, BilliarTR, Curran RD, Cerra FB, Simmons RL, Peitzman AB (1991) Nitrogen oxide levels in patients after trauma and during sepsis. Ann Surg 214: 621–626

    Google Scholar 

  54. Ding A, Nathan CF, Graycar J, Derynck R, Stuehr DJ, Srimal S (1990) Macrophage deactivating factor and transforming growth factors-β1-β2, and β3 inhibit induction of macrophage nitrogen oxide synthesis by IFN-γ. J Immunol 145: 940–944

    PubMed  CAS  Google Scholar 

  55. Nussler AK, Billiar TR (1993) Inflammation, immunoregulation, and inducible nitric oxide synthase. J Leukoc Biol 54: 171–178

    PubMed  CAS  Google Scholar 

  56. Park KS, Lee HW, Hong SY, Shin S, Kim S, Paik WK (1988) Determination of methylated amino acids in human serum by high-performance liquid chromatography. J Chromatogr 440: 225–230

    Article  PubMed  CAS  Google Scholar 

  57. Thiemermann C, Szabo C, Mitchell JA, Vane JR (1993) Vascular hyporeactivity to vasoconstrictor agents and hemodynamic decompensation in hemorrhagic shock is mediated by nitric oxide. Proc Natl Acad Sci USA 90: 267–271

    Article  PubMed  CAS  Google Scholar 

  58. Szabo C, Csaki C, Benyo Z, Reivich M, Kovach AGB (1992) Role of the L-arginine-nitric oxide pathway in the changes in cerebrovascular reactivity following hemorrhagic hypotension and retransfusion. Circ Shock 37: 307–316

    PubMed  CAS  Google Scholar 

  59. Bogle RG, Baydoun AR, Pearson JD, Moncada S, Mann GE (1992) L-Arginine transport is increased in macrophages generating nitric oxide. Biochem J 284: 15–18

    PubMed  CAS  Google Scholar 

  60. Granger DL, Hibbs JB Jr, Perfect JR, Durack DT (1990) Metabolic fate of L-arginine in relation to microbiostatic capability of murine macrophages. J Clin Invest 85: 264–273

    Article  PubMed  CAS  Google Scholar 

  61. Albina JE, Mills CD, Barbul A, Thirkill CE, Henry WL Jr, Mastrofrancesco B, Caldwell MD (1988) Arginine metabolism in wounds. Am J Physiol 254: E459–E467

    PubMed  CAS  Google Scholar 

  62. Harbrecht G, BilliarTR, Stadler J, Demetris AJ, OchoaJB, Curran RD, Simmons RL (1992) Inhibition of nitric oxide synthesis during endotoxemia promotes intrahepatic thrombosis and an oxygen radical-mediated hepatic injury. J Leukoc Biol 52: 390–394

    Google Scholar 

  63. Lieberthal W, McGarry AE, Sheils J, Valeri CR (1991) Nitric oxide inhibition in rats improves blood pressure and renal function during hypovolemic shock. Am J Physiol 261: F868–F872

    PubMed  CAS  Google Scholar 

  64. Zingarelli B, Squadrito F, Altavilla D, Calapai G, Campo GM, Calo M, Saitta A, Caputi AP (1992) Evidence for a role of nitric oxide in hypovolemic hemorrhagic shock. J Cardiovasc Pharmacol 19: 982–986

    Article  PubMed  CAS  Google Scholar 

  65. Klabunde RE, Slayton KJ, Ritger RC (1993) NG-Methyl-L-arginine restores arterial pressure in hemorrhaged rats. Circ Shock 40: 47–52

    PubMed  CAS  Google Scholar 

  66. Symington PA, Ma X-L, Lefer AM (1992) Protective actions of S-nitroso-N-acetylpenicillamine ( SNAP) in a rat model of hemorrhagic shock. Methods Find Exp Clin Pharmacol 14: 789–797

    Google Scholar 

  67. Christopher TA, Ma X-L, Lefer AM (1994) Beneficial actions of S-nitroso-N-acetylpenicillamine, a nitric oxide donor, in murine traumatic shock. Shock 1: 19–24

    Article  PubMed  CAS  Google Scholar 

  68. Carey C, Siegfried MR, Ma X-I, Weyrich AS, Lefer AM (1992) Antishock and endothelial protective actions of a NO donor in mesenteric ischemia and reperfusion. Circ Shock 38: 209–216

    PubMed  CAS  Google Scholar 

Download references

Authors
  1. J. B. Ochoa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. R. Billiar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. B. Peitzman
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Ludwig-Boltzmann-Institut für experimentelle und klinische Traumatologie, Donaueschingenstraße 13, 1200, Wien, Austria

    Günther Schlag  & Heinz Redl  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1995 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Ochoa, J.B., Billiar, T.R., Peitzman, A.B. (1995). The Role of Nitric Oxide in Hemorrhagic Shock and Trauma. In: Schlag, G., Redl, H. (eds) Shock, Sepsis, and Organ Failure — Nitric Oxide. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-79343-1_4

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-79343-1_4

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-79345-5

  • Online ISBN: 978-3-642-79343-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation