Skip to main content
SpringerLink
Log in

Effects of Hypoxia on Inducible Nitric Oxide Synthase (iNOS) in Renal Mesangial Cells

  • Chapter
Role of Nitric Oxide in Sepsis and ADRS

Part of the book series: Update in Intensive Care and Emergency Medicine ((UICM,volume 24))

  • 57 Accesses

Abstract

The effects of hypoxia on the molecular biology and enzyme activity of nitric oxide synthase (NOS) have, until recently, been unclear due to problems measuring nitric oxide (NO), failure to examine the entire NOS pathway, and variable definitions of hypoxia. This chapter describes recent advances in our understanding of the effects of hypoxia on the inducible isoform of nitric oxide synthase (iNOS). The renal mesangial cell was chosen as a model in which to study the effects of hypoxia on iNOS because these cells make NO in sepsis, lack the constitutive form of NOS (cNOS) and, when primed with lipopolysaccharide (LPS), are prolific generators of NO. The importance of examining the iNOS pathway at multiple levels, from induction of messenger ribonucleic acid (mRNA) and iNOS activity to the postsynthetic fate of NO and activation of molecular targets, is explained.

“The great tragedy of Science: The staying of a beautiful hypoyhesis by an ugly fact.”

Thomas Huxley, 1825–1895 (Collected Essays, Ch VIII,“Biogenesis and Abiogenesis”)

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 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. Zimmermann KW (1929) Über den Bau des Glomerulus der menschlichen Niere. Z Mikrosk Anat Forsch 18:520–552

    Google Scholar 

  2. Marinozzi V (1961) Struttura ed istofisiologia del glomerulo. Ati del II Aggiornamen to professionale, Rome. Nefrologia Moderna 5:33–51

    Google Scholar 

  3. Shultz PJ, Raij L (1991) The glomerular mesangium Role in initiation and progression of renal injury. Am J Kidn Dis (Suppl) 17:8–14

    CAS  Google Scholar 

  4. Johnson R, Floege J, Yoshimura A (1992) The activated mesangial cell: A glomerular “myofibroblast”? J Am Soc Nephrol 2:SI90-S197

    Google Scholar 

  5. Latta H (1992) An approach to the stucture and function of the glomerular mesangium. J Am Soc Nephrol 2:S65-S73

    PubMed  CAS  Google Scholar 

  6. Mene P, Cinotti GA, Pugliese F (1992) Signal transduction in mesangial cells. J Am Soc Nephrol 2:S100-S106

    PubMed  CAS  Google Scholar 

  7. Shultz PJ, Schorer AE, Raij L (1990) Effects of endothelium-derived relaxing factor and nitric oxide on rat mesangial cells. Am J Physiol 258:F162-F167

    PubMed  CAS  Google Scholar 

  8. 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 87:3629–3632

    Article  PubMed  CAS  Google Scholar 

  9. Wang Q, Jacobs J, DeLeo J, et al (1991) Nitric oxide hemoglobin in mice and rats in endotoxic shock. Life Sciences 49:PL55-PL60

    Article  PubMed  CAS  Google Scholar 

  10. Raij L, Shultz PJ (1993) Endothelium-derived relaxing factor, nitric oxide: Effects on and production by mesangial cells and the glomerulus. J Am Soc Nephrol 3:1435–1441

    PubMed  CAS  Google Scholar 

  11. Reyes AA, Karl IE, Klahr S (1994) Role of arginine in health and disease. Am J Physiol 36:F331-F346

    Google Scholar 

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

    PubMed  CAS  Google Scholar 

  13. Knowles RG, Moncada S (1994) Nitric oxide synthases in mammals. Biochem J 298:249–258

    PubMed  CAS  Google Scholar 

  14. Geller DA, Nussler AK, Di Silvio M, et al (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 

  15. McQuillan L, Leung GK, Marsden PA, et al (1994) Hypoxia inhibits expression of eNOS via transcriptional and posttranscriptional mechanisms. Am J Physiol 267:H1921-H1927

    PubMed  CAS  Google Scholar 

  16. Archer SL, Freude KA, Schultz P (1995) The effect of graded hypoxia on the induction and function of inducible nitric oxide synthase (iNOS) in rat mesangial cells. Circ Res (In press)

    Google Scholar 

  17. Wiener CM, Dunn A, Sylvester JT (1991) ATP-dependent K+ channels modulate vasoconstrictor responses to severe hypoxia in isolated ferret lungs. J Clin Invest 88:500–504

    Article  PubMed  CAS  Google Scholar 

  18. Buescher P, Perse D, Pillai R, et al (1991) Energy state and vasomotor tone in hypoxic pig lungs. J Appl Physiol 70:1874–1881

    Article  PubMed  CAS  Google Scholar 

  19. Vallet B, Curtis SE, Winn MJ, et al (1994) Hypoxic vasodilation does not require nitric oxide (EDRF/NO) synthesis. J Appl Physiol 76:1256–1261

    Article  PubMed  CAS  Google Scholar 

  20. Hampl V, Weir EK, Archer SL (1994) Endothelium-derived nitric oxide is less important for basal tone regulation in the pulmonary than the renal circulation of the adult rat. J Vase Med Biol 5:22–30

    Google Scholar 

  21. Braughler JM (1983) Soluble guanylate cyclase activation by nitric oxide and its reversal. Biochem Pharmacol 32:811–818

    Article  PubMed  CAS  Google Scholar 

  22. Freeman BA, Crapo JD (1981) Hyperoxia increases oxygen radical production in rat lungs and lung mitochondria. J Biol Chem 256:10986–10992

    PubMed  CAS  Google Scholar 

  23. Archer SL, Nelson DP, Weir EK (1989) Simultaneous measurement of oxygen radicals and pulmonary vascular reactivity in the isolated rat lung. J Appl Physiol 67:1903–1911

    PubMed  CAS  Google Scholar 

  24. Archer SL, Huang J, Henry T, et al (1993) A redox based oxygen sensor in rat pulmonary vasculature. Circ Res 73:1100–1112

    PubMed  CAS  Google Scholar 

  25. Rees DD, Palmer RMJ, Hodson HF, et al (1989) A specific inhibitor of nitric oxide formation from L-arginine attenuates endothelium-dependent relaxation. Br J Pharmacol 96:418–424

    PubMed  CAS  Google Scholar 

  26. Cocks TM, Angus JA (1991) Evidence that contraction of isolated arteries by L-NMMA and NOLA are not due to inhibition of basal EDRF release. J Cardiovasc Pharmacol 17:S159-S164

    Article  CAS  Google Scholar 

  27. Peterson DA, Peterson DC, Archer S, et al (1992) The non-specificity of specific nitric oxide synthase inhibitors. Biochem Biophys Res Commun 187:797–801

    Article  PubMed  CAS  Google Scholar 

  28. Archer SL, Hampl V (1992) NG-monomethyl-L-arginine causes nitric oxide synthesis in isolated arterial rings: Trouble in paradise. Biochem Biophys Res Commun 188:590–596

    Article  PubMed  CAS  Google Scholar 

  29. Shultz PJ, Archer SL, Rosenberg ME (1994) Inducible nitric oxide synthase mRNA and activity in glomerular mesangial cells. Kidney Int 46:683–689

    Article  PubMed  CAS  Google Scholar 

  30. Groves BM, Reeves JT, Sutton JR, et al (1987) Operation Everest II: Elevated high altitude pulmonary resistance unresponsive to oxygen. J Appl Physiol 63:521–530

    PubMed  CAS  Google Scholar 

  31. Adnot S, Raffestin B, Eddahibi S, et al (1991) Loss of endothelium-dependent relaxant activity in the pulmonary circulation of rats exposed to chronic hypoxia. J Clin Invest 87:155–162

    Article  PubMed  CAS  Google Scholar 

  32. Warren JB, Maltby NH, McCormack D, et al (1989) Pulmonary endothelium-derived relaxing factor is impaired in hypoxia. Clin Sci 77:671–676

    PubMed  CAS  Google Scholar 

  33. Emery CJ, Bee D, Barer GR (1981) Mechanical properties and reactivity of vessels in isolated perfused lungs of chronically hypoxic rats. Clin Sci 61:569–580

    PubMed  CAS  Google Scholar 

  34. Isaacson TC, Hampl V, Weir EK, et al (1994) Increased endothelium-derived nitric oxide in hypertensive pulmonary circulation of chronically hypoxic rats. J Appl Physiol 76:933–940

    PubMed  CAS  Google Scholar 

  35. Rengasamy A, Johns RA (1991) Characterization of endothelium-derived relaxing factor/nitric oxide synthase from bovine cerebellum and mechanism of modulation by high and low oxygen tensions. J Pharmacol Exp Ther 259:310–316

    PubMed  CAS  Google Scholar 

  36. Russ RD, Walker BR (1993) Maintained endothelium-dependent pulmonary vasodilation following chronic hypoxia in the rat. J Appl Physiol 74:339–344

    PubMed  CAS  Google Scholar 

  37. Stamler JS, Jaraki J, Osborne D, et al (1992) Nitric oxide circulates in mammalian plasma primarily as an S-nitroso adduct of serum albumin. Proc Natl Acad Sci 89:7674–7677

    Article  PubMed  CAS  Google Scholar 

  38. Ignarro LJ, Fukuto JM, Griscavage JM, et al (1993) Oxidation of nitric oxide in aqueous solution to nitrite but not nitrate: Comparison with enzymatically formed nitric oxide from L-arginine. Proc Natl Acad Sci USA 90:8103–8107

    Article  PubMed  CAS  Google Scholar 

  39. Koppenol WH, Moreno JJ, Pryor WA, et al (1992) Peroxynitrite, a cloaked oxidant formed by nitric oxide and superoxide. Chem Res Toxicol 5:834–842

    Article  PubMed  CAS  Google Scholar 

  40. Zafiriou OC, McFarland M (1980) Determination of trace levels of nitric oxide in aqueous solution. Analytical Chemistry 52:1662–1667

    Article  CAS  Google Scholar 

  41. Moncada S, Palmer RMJ, Higgs EA (1991) Nitric oxide Physiology, pathophysiology and pharmacology. Pharmacol Rev 43:109–141

    PubMed  CAS  Google Scholar 

  42. Archer S (1993) Measurement of nitric oxide in biological models. FASEB J 77:349–360

    Google Scholar 

  43. Murad F, Arnold W, Mittal CK, et al (1979) Properties and regulation of guanylate cyclase and some proposed functions for cyclic GMP. Adv Cyclic Nucleotide Res 11:175–204

    PubMed  CAS  Google Scholar 

  44. Archer SL, Huang JMC, Hampl V, et al (1994) Nitric oxide and cGMP cause vasorelaxation by activation of a charybdotoxin-sensitive K channel by cGMP-dependent protein kinase. Proc Natl Acad Sci USA 91:7583–7587

    Article  PubMed  CAS  Google Scholar 

  45. Twort CHC, van Breemen C (1988) Cyclic guanosine monophosphate-enhanced sequestration of Ca2+ by sarcoplasmic reticulum in vascular smooth muscle. Circ Res 62:961–964

    PubMed  CAS  Google Scholar 

  46. Shultz PJ, Tayeh MA, Marletta MA, et al. (1991) Synthesis and action of nitric oxide in rat glomerular mesangial cells. Am J Physiol 261:F600-F606

    PubMed  CAS  Google Scholar 

  47. Archer SL, Shultz PJ, Warren JB, et al (1995) Preparation of standards and measurement of nitric oxide, nitroxyl and related oxidation products. Methods 7 (In press)

    Google Scholar 

  48. Ahn KY, Mohaupt MG, Madsen KM, et al (1994) In situ hybridization localization of mRNA encoding inducible nitric oxide synthase in rat kidney. Am J Physiol 267:F748-F757

    PubMed  CAS  Google Scholar 

  49. Kozniewska E, Oseka M, Stys T (1992) Effects of endothelium-derived nitric oxide on cerebral circulation during normoxia and hypoxia. J Cereb Blood Flow Metab 12:311–317

    Article  PubMed  CAS  Google Scholar 

  50. Rodman DM, Yamaguchi T, Hasunuma K, et al (1990) Effects of hypoxia on endothelium-dependent relaxation of rat pulmonary artery. Am J Physiol 258:L207-L214

    PubMed  CAS  Google Scholar 

  51. Johns RA, Linden JM, Peach MJ (1989) Endothelium-dependent relaxation and cyclic GMP accumulation in rabbit pulmonary artery are selectively impaired by moderate hypoxia. Circ Res 65:1508–1515

    PubMed  CAS  Google Scholar 

  52. Liu S, Crawley DE, Barnes PJ, et al (1991) Endothelium-derived relaxing factor inhibits hypoxic pulmonary vasoconstriction in rats. Am Rev Respir Dis 143:32–37

    PubMed  CAS  Google Scholar 

  53. Brezis M, Heyman S, Dinour D, et al (1991) Role of NO in renal medullary oxygenation. J Clin Invest 88:390–395

    Article  PubMed  CAS  Google Scholar 

  54. Yu L, Gengaro PE, Niederberger M, et al (1993) Nitric oxide A mediator in rat tubular hypoxia/reoxygenation injury. Proc Natl Acad Sci 91:1691–1695

    Article  Google Scholar 

  55. Thorup C, Persson EG (1994) Inhibition of locally produced NO resets tubuloglomerular feedback mechanism. Am J Physiol 267:F606-F611

    PubMed  CAS  Google Scholar 

  56. Shultz PJ, Tolins JP (1993) Adaptation to increased dietary salt intake in the rat: Role of endogenous nitric oxide. J Clin Invest 91:642–650

    Article  PubMed  CAS  Google Scholar 

  57. Shultz PJ, Raij L (1992) Endogenously synthesized nitric oxide prevents endotoxin induced glomerular thrombosis. J Clin Invest 90:1718–1725

    Article  PubMed  CAS  Google Scholar 

  58. Cattell V, Cook T, Moncada S (1990) Glomeruli synthesize nitrite in experimental nephrotoxic nephritis. Kidney Int 38:1056–1060

    Article  PubMed  CAS  Google Scholar 

  59. Cattel V, Largen P, de Heer E, et al (1991) Glomeruli synthesize nitrite in active Heymann nephritis: The source is infiltrating macrophages. Kidney Int 40:847–851

    Article  Google Scholar 

Download references

Authors
  1. E. Michelakis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P. J. Shultz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. L. Archer
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Surgery, Beth Israel Hospital, 330 Brookline Avenue, 02215, Boston, MA, USA

    M. P. Fink

  2. Department of Anesthesiology and Intensive Care, Lariboisière University Hospital, 2 rue Ambroise Paré, 75475, Paris Cedex 10, France

    Didier Payen

Rights and permissions

Reprints and permissions

Copyright information

© 1995 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Michelakis, E., Shultz, P.J., Archer, S.L. (1995). Effects of Hypoxia on Inducible Nitric Oxide Synthase (iNOS) in Renal Mesangial Cells. In: Fink, M.P., Payen, D. (eds) Role of Nitric Oxide in Sepsis and ADRS. Update in Intensive Care and Emergency Medicine, vol 24. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-79920-4_3

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-79920-4_3

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-79922-8

  • Online ISBN: 978-3-642-79920-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation