The Indian Journal of Pediatrics

, Volume 65, Issue 3, pp 333–345

Nitric oxide: Biological role and clinical uses

  • Mathur S. Kannan
  • Sixto Guiang
  • Dana E. Johnson
Basic and Behavioural Sciences

Abstract

Nitric oxide is a product of the conversion of L-arginine by the enzyme nitric oxide synthase. Nitric oxide is involved in a variety of physiological situations and is produced by many different cell types. It is involved in neurotransmission, maintenance of vascular smooth muscle tone, and cytotoxicity. Nitric oxide has been suggested to play an anti-inflammatory role by inhibiting the expression of the genes for inflammatory cytokines. The pathophysiological role of nitric oxide is also evident in a variety of diseases, including septic shock, asthma, reperfusion injury, etc. Nitric oxide, by stimulating the production of cyclic GMP, relaxes smooth muscles of the cardiovascular, respiratory, gastrointestinal, and genito-urinary systems. Recent studies have provided important information on the use of inhaled nitric oxide for the management of several diseases characterized by the presence of abnormal pulmonary vascular tone, such as persistent pulmonary hypertension of the newborn. This review addresses the biology and clinical uses of inhaled nitric oxide.

Key words

L-arginine Neurotransmission Anti-inflammatory 

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References

  1. 1.
    Moncada S and Higgs A. Mechanisms of disease: the L-arginine-nitric oxide pathway.N Engl J Med, 1993; 329: 2002–2012.PubMedCrossRefGoogle Scholar
  2. 2.
    Furchgott RF and Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine.Nature Lond 1980; 288: 373–376.PubMedCrossRefGoogle Scholar
  3. 3.
    Moncada S, Palmer RM and Higgs EA. Nitric oxide: physiology, pathophysiology, and pharmacology.Pharmacol Rev 1991; 43: 109–142.PubMedGoogle Scholar
  4. 4.
    Mayer B. Biochemistry and molecular pharmacology of nitric oxide synthases. In: Vincent SR, ed.Nitric oxide in the nervous system, Academic Press, 1995; 21–42.Google Scholar
  5. 5.
    Bredt DS and Synder SH. Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme.Proc Natl Acad Sci, USA 1990; 87: 682–685.PubMedCrossRefGoogle Scholar
  6. 6.
    Harald HH, Schmidt W and Walter U. NO at work.Cell 1994; 78: 919–925.CrossRefGoogle Scholar
  7. 7.
    Kannan MS and Johnson DE. Nitric oxide mediates the neural nonadrenergic, noncholinergic relaxation of pig tracheal smooth muscle.Am J Physiol. (Lung Cell. Mol Physiol) 1992; 262: L511-L514.Google Scholar
  8. 8.
    Kobzik L, Bredt DS, Lownestein CJet al. Nitric oxide synthase in human and rat lung: immunocystochemical histochemical localization.Am J Respir Cell Mol Biol 1993; 9: 371–377.PubMedGoogle Scholar
  9. 9.
    Lynons CR, Orloff GJ, and Cunningham JM. Molecular cloning and functional expression of an inducible nitric oxide synthase from a murine macrophage cell line.J Biol Chem 1992; 267: 6360–6374.Google Scholar
  10. 10.
    Cho HJ, Xie QW, Calaycay Jet al. Calmodulin is a subunit of nitric oxide synthase from macrophages.J Exp Med 1992; 176: 599–604.PubMedCrossRefGoogle Scholar
  11. 11.
    Lowenstein CJ, Alley EW, Raval Pet al. Macrophage nitric oxide synthase gene: two upstream regions mediate induction by interferon gamma and lipopolysaccharide.Proc Natl Acad Sci USA 1993; 90: 9730–9734.PubMedCrossRefGoogle Scholar
  12. 12.
    Zhou HL and Torphy TJ. Relationship between cyclic guanosine monophosphate accumulation and relaxation of canine trachealis induced by nitrovasodilators.J Pharmacol Exp Ther 1991; 258: 972–978.PubMedGoogle Scholar
  13. 13.
    Robertson BE, Schubert R, Hescheler J and Nelson MT. cGMP-dependent protein kinase activates Ca-activated K+ channels in cerebral artery smooth muscle cells.Am J Physiol (Cell Physiol) 1993;265: C299-C303.Google Scholar
  14. 14.
    Kannan MS and Johnson DE. Modulation of nitric oxide-dependent relaxation of pig tracheal smooth muscle by inhibitors of guanyl cyclase and calcium activated potassium channels.Life Sci 1995; 56: 2229–2238.PubMedCrossRefGoogle Scholar
  15. 15.
    Bolotina VM, Najibi S, Palacino JJ, Pagano P, and Cohen RA. Nitric oxide directly activates calcium-dependent potassium channels in vascular smooth muscle.Nature 1994; 368: 850–853.PubMedCrossRefGoogle Scholar
  16. 16.
    Kannan MS, Prakash YS, Johnson DE and Sieck GC. Nitric oxide inhibits calcium release from sarcoplasmic reticulum of porcine tracheal smooth muscle cells.Am J Physiol (Lung Cell Mol Phyisol). 1997; 272: L1-L7.Google Scholar
  17. 17.
    Prakash YS, Kannan MS and Sieck GC. Regulation of intracellular calcium oscillations in porcine tracheal smooth muscle cells.Am J Physiol (Cell Physiol) 1997; 272: C966-C975.Google Scholar
  18. 18.
    Prakash YS, Kannan MS and Sieck, GC. Nitric oxide inhibits Ach-induced intracellular calcium oscillations in porcine tracheal smooth muscle.Am J Physiol (Lung Cell Mol Physiol) 1997; 272: L588-L596.Google Scholar
  19. 19.
    Prakash YS, Van Der Heijden HFM, Kannan MS and Sieck GC. Effects of salbutamol on intracellular calcium oscillations in porcine airway smooth muscle.J Appl Physiol 1997; 82: 1836–1843.PubMedGoogle Scholar
  20. 20.
    De Caterina R, Libby P, Peng HB,et al. Nitric oxide decreases cytokine-induced endothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines.J. Clin Invest 1995; 96: 60–68.PubMedCrossRefGoogle Scholar
  21. 21.
    Baeuerle PA and Henkel T. Function and activation of NF-kappa B in the immune system.Annu Rev Immunol 1994; 12: 141–179.PubMedGoogle Scholar
  22. 22.
    Karin M and Hunter T. Transcriptional control by protein phosphorylation: signal transmission from the cell surface to the nucleus.Curr Biol 1995;5: 747–757.PubMedCrossRefGoogle Scholar
  23. 23.
    Peng HB, Libby P and Liao JK. Induction and stabilization of IkB by nitric oxide mediates inhibition of NF-kB.J Biol Chem 1995; 270: 14214–14219.PubMedCrossRefGoogle Scholar
  24. 24.
    Sevransky J, Shaked G, Novogrodsky A,et al. Tyrphostin AG 556 improves survival and reduces TNF levels without affecting endotoxemia or bacteremia in canineE. coli peritonitis.Am Rev Resp Crit Med 1997; 155: A264.Google Scholar
  25. 25.
    Novogrodsky A, Vanichkin A, Patya M Gazit A, Osherov N and Levitzki A. Prevention of lipopolysaccharide-induced lethal toxicity by tyrosine kinase inhibitors.Science 1994;264: 1319–1322.PubMedCrossRefGoogle Scholar
  26. 26.
    Jornes PG, Matthys KE and Bult H. Modulation of nitric oxide synthase activity in macrophages.Mediators of Inflammation 1995; 4: 75–89.CrossRefGoogle Scholar
  27. 27.
    Schulz R, and Triggle CR. Role of NO in vascular smooth muscle and cardiac muscle function.Trends in Pharmacol Sci 1994; 15: 255–259.CrossRefGoogle Scholar
  28. 28.
    Hamid Q, Springall DR, Riveros-Morena V,et al. Induction of nitric oxide synthase in asthma.Lancet 1993; 342: 1510–1513.PubMedCrossRefGoogle Scholar
  29. 29.
    Kharitonov SA, Yates D, Robbins RA, Logan-Sinclair R, Shinebourne E and Barnes PJ. Increased nitric oxide in exhaled air of asthmatic patients.Lancet 1994; 343: 133–135.PubMedCrossRefGoogle Scholar
  30. 30.
    Yates DH, Kharitonov SA, Robbins RA, Thomas PS and Barnes PJ. Effect of nitric oxide synthase inhibitor and a glucocorticosteroid on exhaled nitric oxide.Am J Respir Crit Care Med, 1995; 152: 892–896.PubMedGoogle Scholar
  31. 31.
    Frostell CG and Zapol WM. Inhaled nitric oxide and related nitric oxide donors in the lung: a transatlantic review In: Feelisch M and Stamler JS, ed.Methods in nitric oxide research. John Wiley and Sons Ltd, 1996; 645–659.Google Scholar
  32. 32.
    Wessel DL, Adatia I, Giglia TM. Use of inhaled nitric oxide and acetylcholine in the evaluation of pulmonary hypertension and endothelial function after cardiopulmonary bypass.Circulation 1993; 88: 2128–2138.PubMedGoogle Scholar
  33. 33.
    Mariani G, Barefield ES and Carlo WA. The role of nitric oxide in the treatment of neonatal pulmonary hypertension.Curr Opinion Ped 1996; 8: 118–125.CrossRefGoogle Scholar
  34. 34.
    Anonymous. Inhaled nitric oxide in fullterm and nearly full-term infants with hypoxic respiratory failure. The Neonatal Inhaled Nitric Oxide Study Group.New Engl J Med 1997; 336: 597–604.Google Scholar
  35. 35.
    Roberts JD, Fineman JR, Morin FC,et al. Inhaled nitric oxide and persistent pulmonary hypertension of the newborn. The Inhaled Nitric Oxide Study Group.New Eng J Med 1997; 336: 605–610PubMedCrossRefGoogle Scholar
  36. 36.
    Kinsella JP and Abman SH. Clinical pathophysiology of persistent pulmonary hypertension of the newborn and the role of inhaled nitric oxide therapy.Perinatol 1996; 16: S24-S27.Google Scholar
  37. 37.
    Leveque C, Hamza J, Berg AEet al. Successful repair of a severe left congenital diaphragmatic hernia during continuous inhalation of nitric oxide.Anesthesiology 80: 1171–1175.Google Scholar
  38. 38.
    Karamanoukian HL, Glick PL, Zayek M,et al. Inhaled nitric oxide in congenital hypoplasia of the lungs due to diaphragmatic hernia or oligohydramnios.Pediatrics 1994; 94: 715–718.PubMedGoogle Scholar
  39. 39.
    Karamanoukian HL, Glick, Wilcox DT, Rossman JE, Holm BA and Morin FC. Pathophysiology of congenital diaphragmatic hernia: VIII: Inhaled nitric oxide requires exogenous surfactant therapy in the lamb model of congenital diaphragmatic hernia.J Ped Surg 1995; 30: 1–4.CrossRefGoogle Scholar
  40. 40.
    Warren JB and Higenbottam T. Caution with use of inhaled nitric oxide.Lancet 1996; 348: 629–630.PubMedCrossRefGoogle Scholar

Copyright information

© Department of Pediatrics All India Institute of Medical Science 1998

Authors and Affiliations

  • Mathur S. Kannan
    • 1
    • 2
  • Sixto Guiang
    • 2
  • Dana E. Johnson
    • 2
  1. 1.Department of Veterinary PathoBiologyUniversity of Minnesota College of Veterinary MedicineSt. PaulUSA
  2. 2.Department of PediatricsUniversity of Minnesota College of MedicineSt. PaulUSA

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