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Mediators of Sepsis pp 174–189Cite as

Nitric Oxide as a Mediator of the Vascular Derangements of Sepsis and Endotoxemia

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Part of the book series: Update in Intensive Care and Emergency Medicine ((UICM,volume 16))

Abstract

It is a concept, fundamental to physiology and pharmacology, that if a cellular recognition site exists for a chemical quite foreign to the body, then a similar recognition site, or receptor, might also be the means by which an endogenous ligand, similar to that foreign chemical, also results in cellular activation. Thus, the demonstration of specific recognition sites for morphine led to the search for, and discovery of, endogenous opioid-like peptides. More recently, there has been increasing evidence for the presence within the body of an “endogenous digitalis”. It is now well over a century since T. Lauder Brunton described the beneficial effects of amyl nitrite in patients with angina pectoris, and less than 30 years ago since the precise vascular and cellular mechanisms of action of organic nitrates and nitrites were elucidated. The finding that this depends on activation of soluble guanylyl cyclase within vascular smooth muscle cells, with a subsequent formation of an intracellular second messenger, cyclic 3–5-guanosine monophosphate (cGMP), was one of the factors that led eventually to the discovery of an “endogenous nitrodilator” nitric oxide (NO), the formation of which is responsible for the action of clinically useful nitrodilators such as glyceryl tri-nitrate, nitroprusside and sydnonimines such as molsidomine (and its active metabolite SIN-1) which act on the blood vessel walls by “donating” NO. Endogneous NO is now known to be produced from the amino-acid L-argini-ne in a variety of cells [1] including vascular endothelium [2, 3], macrophages [4], neutrophils [5, 6] and platelets [7, 8]. In endothelial cells, it is this endogenous nitrodilator, NO (or a closely related compound releasing this free radical) that is responsible of the effects of the endothelium-derived relaxing factor (EDRF) originally described by Furchgott and Zawadzki in 1980 [9], who discovered that the ability of acetycholine to relax vascular smooth muscle depended on the integrity of the endothelium and the release from it of a diffusible substance.

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References

  1. Moncada S, Palmer RMJ, Higgs EA (1991) Nitric oxide: Physiology, pathophysiology and pharmacology. Pharmacol Rev 43:109–142

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  3. Salvemini D, Korbut R, Anggard E, Vane JR (1990) Immediate release of a nitric oxide-like factor from bovine aortic endothelial cells by Escherichia coli lipopolysaccharide. Proc Natl Acad Sci USA 87:2593–2597

    Article  PubMed  CAS  Google Scholar 

  4. Hibbs JR 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 

  5. Rimele TJ, Sturm RJ, Adams LM, et al. (1988) Interaction of neutrophils with vascular smooth muscle: Identification of a neutrophil-derived relaxing factor. J Pharmacol Exp Ther 245:102–111

    PubMed  CAS  Google Scholar 

  6. Salvemini D, De Nucci C, Gryglewski RJ, Vane JR (1989) Human neutrophils and mononuclear cells inhibit platelet aggregation by releasing a nitric oxide-like factor. Proc Natl Acad Sci USA 86:6328–6332

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  8. Radomski MW, Palmer RMJ, Moncada S (1990) Characterization of the L-arginine nitric oxide pathway in human platelets. Br J Pharmacol 101:325–328

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  10. Groeneveld ABJ, Bronsveld W, Thijs LG (1986) Hemodynamic determinants of mortality in human septic shock. Surgery 99:140–152

    PubMed  CAS  Google Scholar 

  11. Parratt JR (1989) Alterations in vascular reactivity in sepsis and endotoxemia. In: Vincent JL (ed) Update in intensive care and emergency medicine. Vol 8, Springer, Berlin, pp 299–308

    Google Scholar 

  12. Parratt JR (1973) Myocardial and circulatory effects of E. coli endotoxin; modification of responses to catecholamines. Br J Pharmacol 47:12–25

    PubMed  CAS  Google Scholar 

  13. McCaig DJ, Parratt JR (1980) Reduced myocardial response to calcium during endotoxin shock in the cat. Circ Shock 7:23–30

    PubMed  CAS  Google Scholar 

  14. Parratt JR, Winslow E (1974) The haemodynamic effects of quazodine, a cardiac stimulant, in experimental E. coli endotoxin shock in the cat. Clinical and Experimental Pharm Physiol 1:31–42

    Article  CAS  Google Scholar 

  15. Pomerantz K, Casey L, Fletcher JR, Ramwell PW (1982) Vascular reactivity in endotoxin shock: Effect of lidocaine or indomethacin pretreatment. Adv Shock Res 7:191–198

    PubMed  CAS  Google Scholar 

  16. Parratt JR (1983) Neurohumoral agents and their release in shock. In: Altura AM, Lefer AM, Schumer W (eds) Handbook of Shock and Trauma, Vol 1 (Basic Science), Raven Press, New York, pp 311–336

    Google Scholar 

  17. Bigaud M, Julou-Schaeffer G, Parratt JR, Stoclet JC (1990) Endotoxin-induced impairment of vascular smooth muscle contractions elicited by different mechanisms. Eur J Pharmacol 190:185–192

    Article  CAS  Google Scholar 

  18. Julou-Schaeffer G, Schott C, Parratt JR, Stoclet JC. (1989) Influence of in vivo endotoxin treatment on endothelin-induced contractions of the rat isolated aorta. J Physiol (London) 417:66

    Google Scholar 

  19. Fleming I, Gray GA, Julou-Schaeffer G, Parratt JR, Schott C, Stoclet JC (1990) Impaired vascular reactivity in the rat following endotoxin treatment can be endothelium-independent, yet involves the L-arginine pathway. J Physiol London 423:18

    Google Scholar 

  20. Archer LT, Black MR, Hinshaw LB (1975) Myocardial failure with altered response to adrenaline in endotoxin shock. Br J Pharmacol 54:145–155

    PubMed  CAS  Google Scholar 

  21. Auclair MC, Carli A, Lechat P (1982) Decrease of the hypertensive responses to phenylephrine in the rat submitted to a sublethal dose of E. coli endotoxin. Restoration by indomethacin. J Pharmac (Paris) 13:341

    CAS  Google Scholar 

  22. Auclair MC, Svinareff P, Schmitt H (1986) Vascular a-adrenoceptor blockade of E. coli endotoxin in the rat. Eur J Pharmacol 127:121–124

    Article  PubMed  CAS  Google Scholar 

  23. Auclai MC, Schmitt H (1987) Antagonism by E. coli endotoxin of some cardiovascular effects induced in the rat by two α2-adrenoceptor agonists. Eur J Pharmacol 141:183–290

    Google Scholar 

  24. Fink MP, Homer LD, Fletcher JR (1985) Diminished pressor response to exogenous norepi-nephrine and angiotensin II in septic, unanesthetized rats: Evidence for a prostaglandin-media-ted effect. J Surg Res 38:335–342

    Article  PubMed  CAS  Google Scholar 

  25. Schaller MD, Waeber B, Nussberger J, Brunner HR (1985) Angiotensin II, vasopressin and sympathetic activity in conscious rats with endotoxemia. Am J Physiol 249: 1086–1092

    Google Scholar 

  26. Evequoz D, Waeber B, Corder R, Nussberger J, Gaillard R, Brunner HR (1987) Markedly reduced blood pressure responsiveness in endotoxemic rats; reversal by neuropeptide Y. Life Sci 41:2573–2580

    Article  PubMed  CAS  Google Scholar 

  27. Gray GA, Schott C, Julou-Schaeffer G, Fleming I, Parratt JR, Stoclet JC (1991) An investigation of the effect of inhibitors of the L-arginine pathway on endotoxin-induced vascular hypo-reactivity in vivo. Br J Pharmacol 103:1218–1224

    PubMed  CAS  Google Scholar 

  28. Gray GA, Furman BL, Parratt JR (1990) Endotoxin-induced impairment of vascular reactivity in pithed rat: Role of arachidonic acid metabolites. Circ Shock 31:395–406

    PubMed  CAS  Google Scholar 

  29. Julou-Schaeffer G, Gray GA, Fleming I, Schott C, Parratt JR, Stoclet JC (1990) Loss of vascular responsiveness induced by endotoxin involves the L-arginine pathway. Am J Physiol 295: 1038–1043

    Google Scholar 

  30. Julou-Schaeffer G, Gray GA, Fleming I, Parratt JR, Stoclet JC (1991) Activation of the L-arginine pathway is involved in vascular hyporeactivity induced by endotoxin. J Cardiovasc Pharmacol 17: 207–212

    Article  Google Scholar 

  31. Gillespie JS, McLaren A, Pollock D (1970) A method of stimulating different segments of the autonomic outflow from the spinal column to various organs in the pithed rat and cat. Br J Pharmacol 40:257–267

    PubMed  CAS  Google Scholar 

  32. Guc MO, Gray GA, Furman BL, Parratt JR (1991). Endotoxin-induced impairment of vasode-pressor responses in the pithed rat. Eur J Pharmacol 204:63–70

    Article  PubMed  CAS  Google Scholar 

  33. Smith REA, Palmer RMJ, Moncada S (1991) Coronary vasodilation induced by endotoxin in the rabbit isolated perfused heart is nitric oxide-dependent and inhibited by dexamethasone. Br J Pharmacol 104:5–6

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  35. Kilbourn RG, Gross SS, Jubran A, et al. (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 

  36. Parratt JR, Furman BL, Bouvier C (1991) Endotoxin induced loss of vascular responsiveness; Role of platelet activating factor. Circ Shock 34:375

    Google Scholar 

  37. McKenna TM, Martin FM, Chernow B, Briglia FA (1986) Vascular endothelium contributes to decreased aortic contractility in experimental sepsis. Circ Shock 19:267–273

    PubMed  CAS  Google Scholar 

  38. Wakabayashi I, Hatake K, Kakishita E, Nagai K (1987) Diminution of contractile response of the aorta from endotoxin-injected rats. Eur J Pharmacol 141:117–122

    Article  PubMed  CAS  Google Scholar 

  39. Wakabayashi I, Hatake K, Kakishita E, Nagai K (1987) Effect of phorbol ester on contractile response of aorta from endotoxin rats. Biochem Biophys Res Commun 150:1115–1121

    Article  Google Scholar 

  40. Wakabayashi I, Hatake K, Sakamoto K (1991) Mechanisms ex vivo aortic hyporeactivity in endotoxemic rat. Eur J Pharmacol 199:115–118

    Article  PubMed  CAS  Google Scholar 

  41. Fleming I, Julou-Schaeffer G, Gray GA, Parratt JR, Stoclet JC (1991) Evidence that an L-argi-nine/nitric oxide dependent elevation of tissue cyclic GMP content is involved in depression of vascular reactivity by endotoxin. Br J Pharmacol 103:1047–1052

    PubMed  CAS  Google Scholar 

  42. Martin W, Furchgott RF, Villani GM, Jothianandan D (1989) Depression of contractile responses in rat aorta by spontaneously released endothelium-derived relaxing factor (EDRF). J Pharmacol Exp Ther 237:529–538

    Google Scholar 

  43. Mulsch A, Busse R, Liebau S, Forstermann U (1988) LY 83583 interferes with the release of endothelium-derived relaxing factor and inhibits soluble guanylate cyclase. J Pharmacol Exp Ther 247:283–288

    PubMed  CAS  Google Scholar 

  44. McKenna TM, Reusch DW, Simpkins CO (1988) Macrophage-conditioned medium and inter-leukin 1 suppress vascular contractility. Circ Shock 25:187–196

    PubMed  CAS  Google Scholar 

  45. Fleming I, Gray GA, Julou-Schaeffer G, Parratt JR, Stoclet JC (1990) Incubation with endotoxin activates the L-arginine pathway in vascular tissue. Biochem Biophys Res Commun 171:562–568

    Article  PubMed  CAS  Google Scholar 

  46. Rees DD, Cellk S, Palmer RMJ, Moncada S (1990) Dexamethasone prevents the induction by endotoxin of a nitric oxide synthase and the associated effects of vascular tone: An insight into endotoxin shock. Biochem Biophys Res Commun 173:541–547

    Article  PubMed  CAS  Google Scholar 

  47. Kang Y-H, Williams R (1991) Endotoxin-induced endothelial injury and subendothelial accumulation of fibronectin in rat aorta. Anat Rec 229:86–102

    Article  PubMed  CAS  Google Scholar 

  48. Altura BM, Gebrewold A, Burton RW (1985) Failure of microscopic metarterioles to illicit vasodilator responses to acetylcholine, bradykinin, histamine and substance P after ischemic shock, en-dotoxemia and trauma: Possible role of endothelial cells. Microcirc Endoth Lymph 2:121–134

    CAS  Google Scholar 

  49. Auclair MC, Vernimen C, Carli A, Lechat A (1983) Depressed isoprenaline vascular response in endotoxic rats. Eur J Pharmacol 90:143–150

    Article  PubMed  CAS  Google Scholar 

  50. Guc MO, Furman BL, Parratt JR (1990) Endotoxin-induced impairment of vasopressor and va-sodepressor responses in the pithed rat. Br J Pharmacol 101:913–919

    PubMed  CAS  Google Scholar 

  51. Gray GA, Julou-Schaeffer G, Fleming I, Parratt JR, Stoclet JC (1990) Endothelial function is impaired in aortae from lipopolysaccharide (LPS)-treated rats. J Molec Cell Cardiol 22:8

    Article  Google Scholar 

  52. Beasley D, Cohen RA, Levinsky NG (1990) Endotoxin inhibits contraction of vascular smooth muscle in vitro. Am J Physiol 258: 1187–1192

    Google Scholar 

  53. Parker JL, Keller SR, DeFily DV, Laughlin MH, Novotny MJ, Adams HR (1991) Coronary vascular smooth muscle function in E. coli endotoxemia in dogs. Am J Physiol 260:832–841

    Google Scholar 

  54. Beasley D (1990) Interleukin-1 and endotoxin activate soluble guanylate cyclase in vascular smooth muscle. Am J Physiol 259:38–44

    Google Scholar 

  55. Beasley D, Schwartz JH, Brenner BM (1991) Interleukin-1 induces prolonged L-arginine-de-pendent cyclic guanosine monophosphate and nitrite production in rat vascular smooth muscle cells. J Clin Invest 87:602–608

    Article  PubMed  CAS  Google Scholar 

  56. McKenna TM (1990) Prolonged exposure of rat aorta to low levels of endotoxin in vitro results in impaired contractility; association with vascular cytokine release. J Clin Invest 86:160–168

    Article  PubMed  CAS  Google Scholar 

  57. Fleming I, Gray GA, Parratt JR, Stoclet JC (1991) LPS-induced activation of the L-ar-> ginine/NO pathway in endothelium denuded arterial tissue is time dependent and requires de novo protein synthesis. Br J Pharmacol 102:123

    Google Scholar 

  58. Werner-Felmayer G, Werner ER, Fuchs D, Hausen A, Reibnegger G, Wächter H (1990) Tetra-hydrobiopterin-dependent formation of nitrite and nitrate in murine fibroblasts. J Exp Med 172:1599–1607

    Article  PubMed  CAS  Google Scholar 

  59. Busse R, Mulsch A (1990) Induction of nitric oxide synthase by cytokines in vascular smooth muscle cells. FEBS Lett 275:87–90

    Article  PubMed  CAS  Google Scholar 

  60. Groeneveld ABJ, van Lambalgen AA, van den Bos GC, Bronsveld W, Nauta JJP, Thijs LG (1991) Maldistribution of heterogeneous coronary blood flow during canine endotoxin shock. Cardiovasc Res 25:80–88

    Article  PubMed  CAS  Google Scholar 

  61. McKechnie K, Dean HG, Furman BL, Parratt JR (1985) Plasma catecholamines during endotoxin infusion in conscious unrestrained rats: Effects of adrenal demedullation and/or guanethi-dine treatment. Circ Shock 17:85–94

    PubMed  CAS  Google Scholar 

  62. Hutcheson IR, Whittle BRJ, Boughton-Smith NK (1990) Role of nitric oxide in maintaining vascular integrity in endotoxin-induced acute intestinal damage in the rat. Br J Pharmacol 101:815–820

    PubMed  CAS  Google Scholar 

  63. Wright CE, Rees DD, Moncada S (1992) Protective and pathological roles of nitric oxide in endotoxin shock. Cardiovasc Res 26:48–57

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. J. R. Parratt
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  2. J. C. Stoclet
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Editors and Affiliations

  1. Department of Anesthesiology, Centre Hospitalier, Universitaire de Liège, B-35 Domaine Universitaire du Sart Tilman, 4000, Liège, Belgium

    Maurice Lamy

  2. Department of Intensive Care, Free University Hospital, De Boelelaan 1117, 1007, MS, Amsterdam, The Netherlands

    Lambert G. Thijs

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© 1992 Springer-Verlag Berlin Heidelberg

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Parratt, J.R., Stoclet, J.C. (1992). Nitric Oxide as a Mediator of the Vascular Derangements of Sepsis and Endotoxemia. In: Lamy, M., Thijs, L.G. (eds) Mediators of Sepsis. Update in Intensive Care and Emergency Medicine, vol 16. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-84827-8_12

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  • DOI: https://doi.org/10.1007/978-3-642-84827-8_12

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-84829-2

  • Online ISBN: 978-3-642-84827-8

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