Skip to main content
SpringerLink
Log in
Book cover

The Physiological Genomics of the Critically Ill Mouse pp 159–177Cite as

Inos-Deficient Mice in the Study of Resuscitated Sepsis

  • Chapter

Part of the book series: Basic Science for the Cardiologist ((BASC,volume 16))

Abstract

Septic shock is one of the most frequent causes of morbidity and mortality in intensive care units. Treatment of sepsis begins with support of blood pressure, organ blood flow, and ventilation, along with administration of appropriate antibiotics and eradication of sources of infection. Despite significant advances in therapies available and understanding of pathogenesis, the mortality from septic shock has improved little over the last several decades. The cardinal hemodynamic abnormalities in patients with septic shock include hypotension with a normal or high cardiac output, which result from vasodilation and vascular hyporeactivity to vasoconstrictors. 1 These vascular abnormalities originate in the microvasculature and contribute to multiorgan system failure and death.

This is a preview of subscription content, 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
Hardcover Book
USD   109.99
Price excludes VAT (USA)
  • Durable hardcover 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

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Reference

  1. Hollenberg SM, Parrillo JE. Shock. In: Fauci AS, Braunwald E, Isselbacher KJ, et al., eds. Harrison’s Principles of Internal Medicine. 14 ed. New York: McGraw-Hill, 1997: 214–222.

    Google Scholar 

  2. Hollenberg SM, Cunnion RE. Endothelial and vascular smooth muscle function in sepsis. J. Crit. Care 1994;9:262–280.

    Article  CAS  Google Scholar 

  3. Parrillo JE. Pathogenetic mechanisms of septic shock. N Engl J Med 1993;328:1471–1477.

    Article  PubMed  CAS  Google Scholar 

  4. Beasley D, Cohen RA, Levinsky NG. Interleukin 1 inhibits contraction of vascular smooth muscle. J Clin Invest 1989;83:331–335.

    Article  PubMed  CAS  Google Scholar 

  5. Hollenberg SM, Cunnion RE, Parrillo JE. The effect of tumor necrosis factor on vascular smooth muscle. In vitro studies using rat aortic rings. Chest 1991;100:1133–1137.

    Article  PubMed  CAS  Google Scholar 

  6. Billiau A, Vandekerckhove F. Cytokines and their interactions with other inflammatory mediators in the pathogenesis of sepsis and septic shock. Eur J Clin Invest 1991;21:559–573.

    Article  Google Scholar 

  7. Thiemermann C, Wu C-C, Szabo C, Perretti M, Vane JR. Role of tumour necrosis factor in the induction of nitric oxide synthase in a rat model of endotoxin shock. Br J Pharmacol 1993;110:177–182.

    Article  PubMed  CAS  Google Scholar 

  8. Mathison JC, Wolfson E, Ulevitch RJ. Participation of tumor necrosis factor in the mediation of gram negative bacterial lipopolysaccharide-induced injury in rabbits. J Clin Invest 1988;81:1925–1937.

    Article  PubMed  CAS  Google Scholar 

  9. Tracey KJ, Fong Y, Hesse DG, et al. Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteremia. Nature 1987;330:662–664.

    Article  PubMed  CAS  Google Scholar 

  10. Dinarello CA, Okusawa S, Gelfand JA. Interleukin-1 induces a shock-like state in rabbits: synergism with tumor necrosis factor and the effect of ibuprofen. Prog Clin Biol Res 1989;299:203–215.

    PubMed  CAS  Google Scholar 

  11. French JF, Lambert LE, Dage RC. Nitric oxide synthase inhibitors inhibit interleukin-lbinduced depression of vascular smooth muscle. J Pharm Exp Therapeut 1991;259:260–264.

    CAS  Google Scholar 

  12. Kubes P, Suzuki M, Granger DN. Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci U S A 1991;88:4651–4655.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  14. Moncada S, Palmer RMJ, Higgs EA. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev 1991;43:I09–142.

    Google Scholar 

  15. Forstermann U, Schmidt HHHW, Pollock JS. Isoforms of nitric oxide synthase: characterization and purification from different cell types. Biochem Pharmacol. 1991;42:1849–1856.

    Article  PubMed  CAS  Google Scholar 

  16. Evans T, Carpenter A, Kinderman H, Cohen J. Evidence of increased nitric oxide production in patients with the sepsis syndrome. Circ Shock 1993;41:77–81.

    PubMed  CAS  Google Scholar 

  17. Ochoa JB, Udekwu AO, Billiar TR, et al. Nitrogen oxide levels inpatients after trauma and during sepsis. Ann Surg 1991;214:621–626.

    Article  PubMed  CAS  Google Scholar 

  18. Gomez-Jimenez J, Salgado A, Mourelle M, et al. L-arginine: nitric oxide pathway in endotoxemia and human septic shock. Crit. Care Med. 1995;23:253–258.

    Article  CAS  Google Scholar 

  19. Liu SF, Barnes PJ, Evans TW. Time course and cellular localization of lipopolysaccharide-induced inducible nitric oxide synthase messenger RNA expression in the rat in vivo. Crit Care Med 1997;25:512–518.

    Article  PubMed  CAS  Google Scholar 

  20. Annane D, Sanquer S, Sebille V, et al. Compartmentalised inducible nitric-oxide synthase activity in septic shock. Lancet 2000;355:1143–1148.

    Article  PubMed  CAS  Google Scholar 

  21. Nathan C. Nitric oxide as a secretory product of mammalian cells. FASEB J. 1992;6:3051–3064.

    PubMed  CAS  Google Scholar 

  22. Rees DD. Role of nitric oxide in the vascular dysfunction of septic shock. Biochem Soc Trans 1995;23:1025–1029.

    PubMed  CAS  Google Scholar 

  23. Gray G, Schott C, Julou-Schaeffer G, Fleming I, et al. The effect of inhibitors of the Larginine/nitric oxide pathway on endotoxin-induced loss of vascular responsiveness in anaesthetized rats. Br J Pharmacol 1991;103:1218–1244.

    Article  PubMed  CAS  Google Scholar 

  24. Hollenberg SM, Cunnion RE, Zimmerberg J. Nitric oxide synthase inhibition reverses arteriolar hyporesponsiveness to catecholamines in septic rats. Am.J.Physiol. 1993;264:H660–H663.

    PubMed  CAS  Google Scholar 

  25. Cobb JP, Danner RL. Nitric oxide and septic shock. JAMA 1996;275(15):1192–6.

    Article  Google Scholar 

  26. Grover R, Lopez A, Lorente J, et al. Multi-center, randomized, placebo-controlled, double blind study of the nitric oxide synthase inhibitor 546C88: effect on survival in patients with septic shock. Crit Care Med 1999;27:A33.

    Article  Google Scholar 

  27. Piper RD, Cook DJ, Bone RC, Sibbald WJ. Introducing Critical Appraisal to studies of animal models investigating novel therapies in sepsis. Crit Care Med 1996;24(12):205–970.

    Article  Google Scholar 

  28. Parker MM, Shelhamer JH, Natanson C, Ailing DW, Parrillo JE. Serial cardiovascular variables in survivors and nonsurvivors of human septic shock: heart rate as an early predictor of prognosis. Crit Care Med 1987;15:923–929.

    Article  PubMed  CAS  Google Scholar 

  29. Fleming I, Julou-Schaeffer G, Gray GA, Parratt JR, Stoclet J-C. Evidence that an Larginine/nitric oxide dependent elevation of tissue cyclic GMP content is involved in depression of vascular reactivity by endotoxin. Br J Pharmacol 1991;103:1047–1052.

    Article  PubMed  CAS  Google Scholar 

  30. Julou-Schaeffer G, Gray GA, Fleming I, Schott C, et al. Loss of vascular responsiveness induced by endotoxin involves L-arginine pathway. Am J Physiol 1990;259:H1038–H1043.

    PubMed  CAS  Google Scholar 

  31. Paya D, Gray GA, Fleming I, Stoclet J-C. Effect of dexamethasone on the onset and persistence of vascular hyporeactivity induced by E. coli lipopolysaccharide in rats. Circ Shock 1993;41:103–112.

    CAS  Google Scholar 

  32. Vicaut E, Baudry N. Role of nitric oxide in the hyporesponsiveness to norepinephrine induced by tumor necrosis factor in the microcirculation of skeletal muscle in rats. Circulation 1991;84:11–76.

    Google Scholar 

  33. Thiemermann C, Vane J. Inhibition of nitric oxide synthesis reduces the hypotension induced by bacterial lipopolysaccharides in the rat in vivo. Eur J Pharmacol 1990;182:591–595.

    Article  PubMed  CAS  Google Scholar 

  34. Cobb JP, Natanson C, Hoffman WD, et al. Nw-amino-L-arginine, an inhibitor of nitric oxide synthase, raises vascular resistance but increases mortality rates in awake canines challenged with endotoxin. J Exp Med 1992;176:1175–1182.

    Article  PubMed  CAS  Google Scholar 

  35. Booke M, Hinder F, McGuire R, Traber LD, Traber DL. Nitric oxide synthase inhibition versus norepinephrine for the treatment of hyperdynamic sepsis in sheep. Crit Care Med 1996;24(5):835–44.

    Article  PubMed  CAS  Google Scholar 

  36. Schlag G, Redi H, Gasser H, Davies J, et al. Protective effects of NO synthase inhibition in a baboon model of severe sepsis. Crit. Care Med. 1997;25:A27.

    Google Scholar 

  37. Robertson FM, Offner PJ, Ciceri DP, et al. Jr. Detrimental hemodynamic effects of nitric oxide synthase inhibition in septic shock. Arch Surg 1994;129:149–156.

    Article  PubMed  CAS  Google Scholar 

  38. Lorente JA, Landin L, De Pablo R, Renes E, Liste D. L-arginine pathway in the sepsis syndrome. Crit Care Med 1993;21:1287–1295.

    Article  PubMed  CAS  Google Scholar 

  39. Petros A, Lamb G, Leone A, Moncada S, et al. Effects of a nitric oxide synthase inhibitor in humans with septic shock. Cardiovasc Res 1995;28:34–39.

    Article  Google Scholar 

  40. Sundrani R, Easington CR, Mattoo A, Parrillo JE, Hollenberg SM. Nitric oxide synthase inhibition increases venular leukocyte rolling and adhesion in septic rats. Crit Care Med 2000;28(8):2898–903.

    Article  PubMed  CAS  Google Scholar 

  41. Filep JG, Delalandre A, Beauchamp M. Dual role for nitric oxide in the regulation of plasma volume and albumin escape during endotoxin shock in conscious rats. Circ Res 1997;81:840–847.

    Article  PubMed  CAS  Google Scholar 

  42. Liaudet L, Rosselet A, Schaller MD, Markert M, Perret C, Feihl F. Nonselective versus selective inhibition of inducible nitric oxide synthase in experimental endotoxic shock. J Infect Dis 1998;177:127–132.

    Article  PubMed  CAS  Google Scholar 

  43. Aranow JS, Zhuang J, Wang H, Larkin V, Smith M, Fink MP. A selective inhibitor of inducible nitric oxide synthase prolongs survival in a rat model of bacterial peritonitis: comparison with two nonselective strategies. Shock 1996;5:116–121.

    Article  PubMed  CAS  Google Scholar 

  44. MacMicking JD, Nathan C, Hom G, et al. Altered responses to bacterial infection and endotoxic shock in mice lacking inducible nitric oxide synthase. Cell 1995;81:641–650.

    Article  PubMed  CAS  Google Scholar 

  45. Laubach VE, Shesely EG, Smithies O, Sherman PA. Mice lacking inducible nitric oxide synthase are not resistant to lipopolysaccharide-induced death. Proc Natl Acad Sci U S A 1995;92(23):10688–92.

    Article  PubMed  CAS  Google Scholar 

  46. Wei XQ, Charles IG, Smith A, et al. Altered immune responses in mice lacking inducible nitric oxide synthase. Nature 1995;375(6530):408–11.

    Article  PubMed  CAS  Google Scholar 

  47. Hollenberg SM, Dumasius A, Easington C, Colilla SA, Neumann A, Parrillo JE. Characterization of a hyperdynamic murine model of resuscitated sepsis using echocardiography. Am J Resp Crit Care Med 2001;164:891–895.

    PubMed  CAS  Google Scholar 

  48. Hollenberg SM, Piotrowski MJ, Parrillo JE. Nitric oxide synthase inhibition reverses arteriolar hyporesponsiveness to endothelin-1 in septic rats. Am J Physiol 1997;272(3 Pt 2):R969–R974.

    PubMed  CAS  Google Scholar 

  49. Hollenberg SM, Tangora JJ, Piotrowski MJ, Easington C, Parrillo JE. Impaired microvascular vasoconstrictive responses to vasopressin in septic rats. Crit Care Med 1997;25(5):869–73.

    Article  PubMed  CAS  Google Scholar 

  50. Ganeshram V, Piotrowski MJ, Parrillo JE, Hollenberg SM. Nitric oxide synthase inhibition reverses impaired arteriolar responsiveness to angiotensin II in septic rats. J Investig Med 1995;43:241A.

    Google Scholar 

  51. Hollenberg SM, Easington CR, Osman J, Broussard M, Parrillo JE. Effects of nitric oxide synthase inhibition on microvascular reactivity in septic mice. Shock 1999;12:262–267.

    Article  PubMed  CAS  Google Scholar 

  52. Broussard MD, Parrillo JE, Prancan AV, Hollenberg SM. Inducible nitric oxide synthase (iNOS) deficient septic mice show improved microvascular responsiveness to endothelin1. FASEB J 2000;14:A404.

    Google Scholar 

  53. Hollenberg SM, Easington CR, Osman J, Broussard M, Belue R, Parrillo JE. The effect of selective and nonselective nitric oxide synthase inhibition on microvascular catecholamine reactivity in septic mice. Crit Care Med 1999;29:Al26.

    Google Scholar 

  54. Hollenberg SM, Broussard M, Osman J, Easington CE, Parrillo JE. Improved microvascular catecholamine reactivity in iNOS-deficient septic mice. FASEB J 1999;13 (II):A1067.

    Google Scholar 

  55. Lush CW, Kvietys PR. Microvascular dysfunction in sepsis. Microcirculation 2000;7(2):83–101.

    PubMed  CAS  Google Scholar 

  56. Parent C, Eichacker PQ. Neutrophil and endothelial cell interactions in sepsis. The role of adhesion molecules. Infect Dis Clin North Am 1999;13(2):427–447.

    Article  PubMed  CAS  Google Scholar 

  57. Hickey MJ, Sharkey KA, Sihota EG, et al. Inducible nitric oxide synthase-deficient mice have enhanced leukocyte-endothelium interactions in endotoxemia. FASEB J 1997;11:955–964.

    PubMed  CAS  Google Scholar 

  58. Hickey MJ, Granger DN, Kubes P. Inducible nitric oxide synthase (iNOS) and regulation of leucocyte/endothelial cell interactions: studies in iNOS-deficient mice. Acta Physiol Scand 2001;173(1):119–26.

    Article  CAS  Google Scholar 

  59. Lush CW, Cepinskas G, Sibbald WJ, Kvietys PR. Endothelial E- and P-selectin expression in iNOS- deficient mice exposed to polymicrobial sepsis. Am J Physiol Gastrointest Liver Physiol 2001;280(2):G291–7.

    PubMed  CAS  Google Scholar 

  60. Hickey MJ, Sihota E, Amrani A, et al. Inducible nitric oxide synthase (iNOS) in endotoxemia: chimeric mice reveal different cellular sources in various tissues. FASEB J 2002;16(9):1141–3.

    PubMed  CAS  Google Scholar 

  61. Cruz K, Parrillo JE, Hollenberg SM. Demonstration of decreased microvascular permeability in inducible nitric oxide synthase deficient septic mice by in vivo fluorescence videomicroscopy. Crit Care Med 2002;29:A46.

    Google Scholar 

  62. Seely AJ, Christou NV. Multiple organ dysfunction syndrome: exploring the paradigm of complex nonlinear systems. Crit Care Med 2000;28(7):2193–200.

    Article  PubMed  CAS  Google Scholar 

  63. Godin PJ, Buchman TG. Uncoupling of biological oscillators: a complementary hypothesis concerning the pathogenesis of multiple organ dysfunction syndrome. Crit Care Med 1996;24(7):1107–16.

    Article  PubMed  CAS  Google Scholar 

  64. Manela D, Cruz K, Cohen E, Parrillo JE, Hollenberg SM. Blood pressure variability in a murine model of sepsis. Crit Care Med 2002;29:A43.

    Google Scholar 

  65. Manela D, Cohen E, Cruz K, Hollenberg SM. Blood pressure variability in inducible nitric oxide synthase-deficient septic mice. J Investig Med 2002;50:169A.

    Google Scholar 

  66. Gonzalez C, Fernandez A, Martin C, Moncada S, Estrada C. Nitric oxide from endothelium and smooth muscle modulates responses to sympathetic nerve stimulation: implications for endotoxin shock. Biochem Biophys Res Commun 1992;186:150–156.

    Article  PubMed  CAS  Google Scholar 

  67. Zanzinger J, Czachurski J, Seller H. Inhibition of sympathetic vasoconstriction is a major principle of vasodilation by nitric oxide in vivo. Circ Res 1994;75:1073–1077.

    Article  PubMed  CAS  Google Scholar 

  68. Winterbourn CC, Buss IH, Chan TP, Plank LD, Clark MA, Windsor JA. Protein carbonyl measurements show evidence of early oxidative stress in critically ill patients. Crit Care Med 2000;28:143–149.

    Article  PubMed  CAS  Google Scholar 

  69. O’Donnell VB, Freeman BA. Interactions between nitric oxide and lipid oxidation pathways: implications for vascular disease. Circ Res 2001;88(1):12–21.

    Article  PubMed  Google Scholar 

  70. Miles AM, Bohle DS, Glassbrenner PA, Hansert et al. Modulation by superoxide-dependent oxidation and hydroxylation reactions by nitric oxide. J Biol Chem 1996;271:40–47.

    Article  PubMed  CAS  Google Scholar 

  71. Cai H, Harrison DG. Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res 2000;87:840–844.

    Article  PubMed  CAS  Google Scholar 

  72. Padgett CM, Whorton AR. Regulation of cellular thiol redox status by nitric oxide. Cell Biochem Biophys 1995;27(3):157–77.

    Article  PubMed  CAS  Google Scholar 

  73. Carbonell LF, Nadal JA, Llanos MC, Hernandez I, et al. Depletion of liver glutathione potentiates the oxidative stress and decreases nitric oxide synthesis in a rat endotoxin shock model. Crit Care Med 2000;28:2002–2006.

    Article  PubMed  CAS  Google Scholar 

  74. Suematsu M, Schmid-Schonbein GW, Chavez-Chavez RH, et al. In vivo visualization of oxidative changes in microvessels during neutrophil activation. Am J Physiol 1993;264:H881–H891.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Coronary Care Unit, Cooper Hospital/University Medical Center, Camden, USA

    Steven M. Hollenberg

Authors
  1. Steven M. Hollenberg
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Physiology Academic Medical Center, University of Amsterdam, The Netherlands

    Can Ince

Rights and permissions

Reprints and permissions

Copyright information

© 2004 Springer Science+Business Media New York

About this chapter

Cite this chapter

Hollenberg, S.M. (2004). Inos-Deficient Mice in the Study of Resuscitated Sepsis. In: Ince, C. (eds) The Physiological Genomics of the Critically Ill Mouse. Basic Science for the Cardiologist, vol 16. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0483-2_12

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-0483-2_12

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5099-6

  • Online ISBN: 978-1-4615-0483-2

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation