Skip to main content
Log in

The Use of Selective Inhibitors of Inducible Nitric Oxide Synthase in Septic Shock

  • Published:
Sepsis

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

References

  1. Thiemermann C, Vane JR. Inhibition of nitric oxide synthesis reduces the hypotension induced by bacterial lipopolysaccharide in the rat. Eur J Pharmacol 1990; 182: 591–5.

    Google Scholar 

  2. Kilbourn RG, Juburan A, Gross SS, et al. Reversal of endotoxin-mediated shock by NG-monomethyl-L-arginine, an inhibitor of nitric oxide synthesis. Biochem Biophys Res Commun 1990; 172:1132–8.

    Google Scholar 

  3. Kilbourn RG, Gross SS, Jubran A, et al. NG-methyl-L-arginine inhibits tumour necrosis factor-induced hypotension: implications for the involvement of nitric oxide. Proc Natl Acad Sci USA 1990; 87:3629–32.

    Google Scholar 

  4. Julou-Schaeffer G, Gray GA, Fleming I, Schott C, Parratt JR, Stoclet JC. Loss of vascular responsiveness induced by endotoxin involves the L-arginine pathway. Am J Physiol 1990; 259:H1038–43.

    Google Scholar 

  5. Rees DD, Cellek, S, Palmer RMJ, Moncada S. Dexamethasone prevents the induction of nitric oxide synthase and the associated effects on the vascular tone: an insight into endotoxic shock. Biochem Biophys Res Commun 1990; 173: 541–47.

    Google Scholar 

  6. Billiar TR, Curran RD, Harbrecht BG, Stuehr DJ, Demetris AJ, Simmons RI. Modulation of nitrogen oxide synthesis in vivo: NG-monomethyl-L-arginine inhibits endotoxin-induced nitrite/nitrate biosynthesis while promoting hepatic damage. J Leuk Biol 1990; 48:565–569.

    Google Scholar 

  7. Thiemermann C. The role of L-arginine:nitric oxide pathway in circulatory shock. Adv Pharmacol 1994; 28:45–79.

    Google Scholar 

  8. Szabo C. Alterations in nitric oxide production in various forms of circulatory shock. Horizon 1995; 1:2–32.

    Google Scholar 

  9. Rees DD. Role of nitric oxide in the vascular dysfunction in septic shock. Biochem Soc Trans 1995; 23:1025–9.

    Google Scholar 

  10. Wu CC, Ruetten H, Thiemermann C. Comparison of the effects of aminoguanidine and NG-nitro-L-arginine methyl ester on the multiple organ dysfunction caused by endotoxemia in the rat. Eur J Pharmacol 1996; 300:99–104.

    Google Scholar 

  11. Morris SM, Billiar TR. New insights into the regulation of inducible nitric oxide synthase. Am J Physiol 1994; 266: E829–39.

    Google Scholar 

  12. Szabo C, Thiemermann C. Regulation of the expression of the inducible isoform of nitric oxide synthase. Adv Pharmacol 1995; 34:113–54.

    Google Scholar 

  13. Southan GJ, Szabo C. Selective pharmacological inhibition of distinct nitric oxide synthase isoforms. Biochem Pharmacol 1996; 51:383–394.

    Google Scholar 

  14. Gross SS, Stuehr DJ, Aisaka K, Jaffe EA Levi R, Griffith OW. Macrophage and endothelial nitric oxide synthesis: cell-type selective inhibition by NG-aminoarginine, NG-nitroarginine and NG-methyl-arginine. Biochem Biophys Res Commun 1990; 170:96–103.

    Google Scholar 

  15. Feldmann PL, Griffith OW, Honh H, Stuehr D. Irreversible inactivation of macrophage and brain nitric oxide synthase by L-NG-methyl arginine requires NADPH-dependent hydroxylation. J Med Chem 1993; 36:491–496.

    Google Scholar 

  16. Thiemermann C, Ruetten H, Wu CC, Vane JR. The multiple organ dysfunction syndrome caused by endotoxin in the rat: Attenuation of liver dysfunction by inhibitors of nitric oxide synthase. Br J Pharmacol 1995; 116:2845–2851.

    Google Scholar 

  17. Millar CGM, Thiemermann C. Intrarenal hemodynamics and renal dysfunction in endotoxemia: Effects of nitric oxide synthase inhibition. Br J Pharmacol 1997; In press.

  18. Shultz PJ, Raij L. Endogenously synthetized nitric oxide prevents endotoxin-induced glomerular thrombosis. J Clin Invest 1992; 90:1718–25.

    Google Scholar 

  19. Rees DD, Monkhouse JE, Deakin AM, Cambride D, Moncada S. The role of nitric oxide in a conscious mouse model of endotoxin shock. Br J Pharmacol 1995; 114:123P.

    Google Scholar 

  20. Meyer J, Traber LD, Nelson S, et al. Reversal of hyperdynamic response to continuous endotoxin administration by inhibition of NO synthesis. J Appl Physiol 1992; 73:324–328.

    Google Scholar 

  21. Meyer J, Lentz CW, Stothert JC, Traber LD, Herndon DN, Traber DL. Effects of nitric oxide synthesis inhibition in hyperdynamic endotoxemia. Crit Care Med 1994; 22: 306–312.

    Google Scholar 

  22. Strohmeier W, Werner ER, Redl H, Wachter H, Schlag G. Plasma nitrate and pteridine levels in experimental bacteremia in baboons. Pteridines 1995; 6:8–11.

    Google Scholar 

  23. Corbett JA, Tilton RG, Chang, K, et al. Aminoguanidine, a novel inhibitor of nitric oxide formation, prevents diabetic vascular dysfunction. Diabetes 1992; 41:552–558.

    Google Scholar 

  24. Misko TP, Moore WM, Kasten TP, et al. Selective inhibition of the inducible nitric oxide synthase by aminoguanidine. Eur J Pharmacol 1993; 233:119–125.

    Google Scholar 

  25. Griffith MJ, Messent M, MacAllister RJ, Evans TW. Aminoguanidine selectively inhibits inducible nitric oxide synthase. Br J Pharmacol 1993; 110:963–8.

    Google Scholar 

  26. Joly GA, Ayres M, Chelly F, Kilbourn RG. Effects of NG-methyl-L-arginine, NG-nitro-L-arginine and aminoguanidine on constitutive and inducible nitric oxide synthase in rat aorta. Biochem Biophys Res Commun 1994; 199:147–54.

    Google Scholar 

  27. Wu CC, Chen SJ, Szabo C, Thiemermann C, Vane JR. Aminoguanidine attenuates the delayed circulatory failure and improves survival in rodent models of endotoxic shock. Br J Pharmacol 1995; 114:1666–1672.

    Google Scholar 

  28. Wolff DJ, Lubeskie, A. Aminoguanidine is an isoform-selective, mechanism-based inactivator of nitric oxide synthase. Arch Biochem Biophys 1995; 316:290–301.

    Google Scholar 

  29. Ruetten H, Southan GJ, Abate A, Thiemermann C. Attenuation of the multiple organ dysfunction caused by endotoxin by 1-amino-2-hydroxy-guanidine, a potent inhibitor of inducible nitric oxide synthase. Br J Pharmacol 1996; 118:261–270.

    Google Scholar 

  30. Seo HG, Fujiwara N, Kaneto H, Asashi M, Fujii J, Taniguchi N. Effect of the nitric oxide synthase inhibitor, S-ethylisothiourea, on cultured cells and cardiovascular functions of normal and lipopolysaccharide-treated rabbits. J Biochem 1996; 119:553–8.

    Google Scholar 

  31. Muller CM, Scierka A, Stiller RL, et al. Nitric oxide mediates hepatic cytochrome P450 dysfunction induced by endotoxin. Anesthesiology 1996; 84:1435–42.

    Google Scholar 

  32. Ou J, Molina L, Kim YM, Billiar TR. Excessive NO production does not account for the inhibition of hepatic gluconeogenesis in endotoxemia. Am J Physiol 1996; 271:621–8.

    Google Scholar 

  33. Klabunde RE, Coston AF. Nitric oxide synthase inhibition does not prevent cardiac depression in endotoxic shock. Shock 1995; 3:73–8.

    Google Scholar 

  34. Sorrells DL, Friend C, Koltuksuk U, et al. Inhibition of nitric oxide with aminoguanidine reduces bacterial translocation after endotoxin challenge in vivo. Arch Surg 1996; 131:1155–63.

    Google Scholar 

  35. Boje KM. Inhibition of nitric oxide synthase attenuates blood-brain barrier disruption during experimental meningitis. Brain Res 1996; 720:75–83.

    Google Scholar 

  36. Arkovitz MS, Wispe JR, Garcia VF, Szabo C. Selective inhibition of the inducible isoform of nitric oxide synthase prevents pulmonary transvascular flux during acute endotoxemia. J Pediatr Surg 1996; 31:1009–15.

    Google Scholar 

  37. Bieganski T, Kusche J, Lorenz W, Hesterberg R, Stahlknecht CD, Feussner KD. Distribution and properties of human diamine oxidase and its relevance for the histamine catabolism. Biochem Biophys Acta 1983; 756:196–203.

    Google Scholar 

  38. Seiler N, Bolkenius FN, Knodgen B. The influence of catabolic reactions on polyamine excretion. Biochem J 1985; 225:219–226.

    Google Scholar 

  39. Ou P, Wolff SP. Aminoguanidine: A drug proposed for prophylaxis in diabetes inhibits catalase and generates hydrogen peroxide in vitro. Biochem Pharmacol 1993; 46:1139–44.

    Google Scholar 

  40. Picard S, Parthasarathy S, Fruebis J, Witzum JL. Aminoguanidine inhibits oxidative modification of low density lipoprotein and the subsequent increase in uptake by macrophage scavenger receptors. Proc Natl Acad Sci USA 1992; 89:6876–80.

    Google Scholar 

  41. Ruetten H, Thiemermann, C. Prevention of the expression of inducible nitric oxide synthase by aminoguanidine or aminoethylisothiourea in macrophages and in the rat. Biochem Biophys Res Commun 1996; 225:525–530.

    Google Scholar 

  42. Garvey PE, Oplinger JA, Tanoury GJ, et al. Potent and selective inhibition of human nitric oxide synthases. Inhibition by non-amino acid isothioureas. J Biol Chem 1994; 269: 26669–76.

    Google Scholar 

  43. Szabo C, Southan G, Thiemermann C. Beneficial effects and improved survival in rodent models of septic shock with S-methyl-isothiourea sulfate, a novel, potent and selective inhibitor of inducible nitric oxide synthase. Proc Natl Acad Sci USA 1994; 91:12472–76.

    Google Scholar 

  44. Southan G, Szabo C, Thiemermann C. Isothioureas: potent inhibitors of nitric oxide synthases with variable isoform selectivity. Br J Pharmacol 1995; 114:510–16.

    Google Scholar 

  45. Southan GJ, Zingarelli B, O'Conner M, Salzman AL, Szabo C. Spontaneous rearrangement of aminoalkylisothioureas into mercaptoalkylguanidines, a novel class of nitric oxide synthase inhibitors with selectivity towards the inducible isoform. Br J Pharmacol 1996; 117:619–32.

    Google Scholar 

  46. Martinez MC, Muller B, Stoclet JC, Andriantsitohaina R. Alteration by lipopolysaccharide of the relationship between intracellular calcium levels and contraction in rat mesenteric artery. Br J Pharmacol 1996; 118:1218–22.

    Google Scholar 

  47. Saetre T, Gundersen Y, Thiemermann C, Lilleansen P, Aasen AO. Aminoethyl-isothiourea, a selective inhibitor of inducible nitric oxide synthase activity, improves liver circulation and oxygen metabolism in a porcine model of endotoxaemia. Shock 1997; in press.

  48. Muraki T, Fujii E, Okada M, Horikawa H, Irie K, Ohba K. Effect of S-ethyl-isothiourea, a putative inhibitor of inducible nitric oxide synthase, on mouse skin vascular permeability. Jpn J Pharmacol 1996; 70:269–71.

    Google Scholar 

  49. Vromen A, Szabo C, Southan GJ, Salzman AL. Effects of S-isopropyl isothiourea, a potent inhibitor of nitric oxide synthase, in severe hemorrhagic shock. J Appl Physiol 1996; 81:707–15.

    Google Scholar 

  50. Southan GJ, Szabo C, O'Conner MP, Salzman AC, Thiemermann C. Amidines are potent inhibitors of nitric oxide synthases: Preferential inhibition of the inducible isoform. Eur J Pharmacol 1995; 291:311–318.

    Google Scholar 

  51. Garvey EP, Oplinger JA, Furfine ES, et al. 1400W is a slow, tight binding, and highly selective inhibitor of inducible nitric oxide synthase in vitro and in vivo. J Biol Chem 1997; 272:4959–63.

    Google Scholar 

  52. Wei X, Charles IG, Smith, A et al. Altered immune responses in mice lacking inducible nitric oxide synthase. 1995; 375:408–411.

    Google Scholar 

  53. 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; 82:641–650.

    Google Scholar 

  54. Laubach VE, Sheseley EG, Smithies O, Sherman PA. Mice lacking inducible nitric oxide synthase are not resistant to lipopolysaccharide-induced death. Proc Natl Acad Sci USA 1995; 92:10668–92.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Thiemermann, C. The Use of Selective Inhibitors of Inducible Nitric Oxide Synthase in Septic Shock. Sepsis 1, 123–129 (1998). https://doi.org/10.1023/A:1009780509335

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1009780509335

Keywords

Navigation