Journal of Biomedical Science

, Volume 11, Issue 4, pp 534–537 | Cite as

Decreased total nitric oxide production in patients with duchenne muscular dystrophy

  • Takefumi Kasai
  • Kazuhiro Abeyama
  • Teruto Hashiguchi
  • Hidetoshi Fukunaga
  • Mitsuhiro Osame
  • Kuro Maruyama
Short Communication


Plasma nitric oxide (NO) levels in Duchenne muscular dystrophy (DMD) patients were significantly lower than those observed in both healthy controls and in patients with other neuromuscular disorders. The correlation between NO level and ejection fraction was significant (r=−0.384, p=0.0391) in the DMD group. Disruption of NO systems may contribute to the development of muscular dystrophy and have implications for therapeutic strategies.

Key Words

Duchenne muscular dystrophy Dystrophin Nitric oxide nNOS 


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  1. 1.
    Azzena GB, Mancinelli R. Nitric oxide regenerates the normal colonic peristaltic activity in mdx dystrophic mouse. Neurosci Lett 261:9–12;1999.CrossRefPubMedGoogle Scholar
  2. 2.
    Baccari MC, Romagnani P, Calamai F. Impaired nitrergic relaxations in the gastric fundus of dystrophic (mdx) mice. Neurosci Lett 282:105–108;2000.CrossRefPubMedGoogle Scholar
  3. 3.
    Barohn RJ, Levine EJ, Olson JO, Mendell JR. Gastric hypomotility in Duchenne's muscular dystrophy. N Engl J Med 319:15–18;1988.PubMedGoogle Scholar
  4. 4.
    Bia BL, Cassidy PJ, Young ME, Rafael JA, Leighton B, Davies KE, Radda GK, Clarke K. Decreased myocardial nNOS, increased iNOS and abnormal ECGs in mouse models of Duchenne muscular dystrophy. J Mol Cell Cardiol 31:1857–1862;1999.CrossRefPubMedGoogle Scholar
  5. 5.
    Blake DJ, Kroger S. The neurobiology of Duchenne muscular dystrophy: Learning lessons from muscle? Trends Neurosci 23:92–99;2000.CrossRefPubMedGoogle Scholar
  6. 6.
    Brenman JE, Chao DS, Xia H, Aldape K, Bredt DS. Nitric oxide synthase complexed with dystrophin and absent from skeletal muscle sarcolemma in Duchenne muscular dystrophy. Cell 82:743–752;1995.CrossRefPubMedGoogle Scholar
  7. 7.
    Brenman JE, Chao DS, Gee SH, McGee AW, Craven SE, Santillano DR, Wu Z, Huang F, Xia H, Peters MF, Froehner SC, Bredt DS. Interaction of nitric oxide synthase with the postsynaptic density protein PSD-95 and alphal-syntrophin mediated by PDZ domains. Cell 84:757–767;1996.CrossRefPubMedGoogle Scholar
  8. 8.
    Chang WJ, Iannaccone ST, Lau KS, Masters BSS, McCabe TJ, McMillan K, Padre RC, Spencer MJ, Tidball JG, Stull JT. Neuronal nitric oxide synthase and dystrophin-deficient muscular dystrophy. Proc Natl Acad Sci USA 93:9142–9147;1996.CrossRefPubMedGoogle Scholar
  9. 9.
    Chao DS, Gorospe JR, Brenman JE, Rafael JA, Peters MF, Froehner SC, Hoffman EP, Chamberlain JS, Bredt DS. Selective loss of sarcolemmal nitric oxide synthase in Becker muscular dystrophy. J Exp Med 184:609–618;1996.CrossRefPubMedGoogle Scholar
  10. 10.
    Crosbie RH. NO vascular control in Duchenne muscular dystrophy. Nat Med 7:27–29;2001.CrossRefPubMedGoogle Scholar
  11. 11.
    Engel AG, Banker BQ. Myology: Basic and Clinical. New York, McGraw-Hill, 1994.Google Scholar
  12. 12.
    Evans HG, Lewis MJ, Shah AM. Interleukin-1-beta modulates myocardial contraction via dexamethasone sensitive production of nitric oxide. Cardiovasc Res 27:1486–1490;1993.PubMedGoogle Scholar
  13. 13.
    Finkel MS, Oddis CV, Jacob TD, Watkins SC, Hattler BG, Simmons RL. Negative inotropic effects of cytokines on the heart mediated by nitric oxide. Science 257:387–389;1992.PubMedGoogle Scholar
  14. 14.
    Gaffney JF, Kingston WJ, Metlay LA, Gramiak R. Left ventricular thrombus and systemic emboli complicating the cardiomyopathy of Duchenne's muscular dystrophy. Arch Neurol 46:1249–1252;1989.PubMedGoogle Scholar
  15. 15.
    Gardiner SM, Compton AM, Bennett T, Palmer RM, Moncada S. Control of regional blood flow by endothelium-derived nitric oxide. Hypertension 15:486–492;1990.PubMedGoogle Scholar
  16. 16.
    Gucuyener K, Ergenekon E, Erbas D, Pinarli G, Serdaroglu A. The serum nitric oxide levels in patients with Duchenne muscular dystrophy. Brain Dev 22:181–183;2000CrossRefPubMedGoogle Scholar
  17. 17.
    Guslandi M. Nitric oxide: An ubiquitous actor in the gastrointestinal tract. Dig Dis 12:28–36;1994.PubMedGoogle Scholar
  18. 18.
    Hashida-Okumura A, Okumura N, Iwamatsu A, Buijs RM, Romijn HJ, Nagai K. Interaction of neuronal nitric-oxide synthase with alphalsyntrophin in rat brain. J Biol Chem 274:11736–11741;1999.CrossRefPubMedGoogle Scholar
  19. 19.
    Huang KL, Wu CP, Kang BH, Lin YC. Chronic hypoxia attenuates nitric oxide-dependent hemodynamic responses to acute hypoxia. J Biomed Sci 9:206–212;2002.PubMedGoogle Scholar
  20. 20.
    Kobzik L, Reid MB, Bredt DS, Stamler JS, Nitric oxide in skeletal muscle. Nature 372:546–548;1994.CrossRefPubMedGoogle Scholar
  21. 21.
    Lau KS, Grange RW, Chang WJ, Kamm KE, Sarelius I, Stull JT. Skeletal muscle contractions stimulate cGMP formation and attenuate vascular smooth muscle myosin phosphorylation via nitric oxide. FEBS Lett 431:71–74;1998.CrossRefPubMedGoogle Scholar
  22. 22.
    Lee KH, Baek MY, Moon KY, Song WK, Chung CH, Ha DB, Kang MS. Nitric oxide as a messenger molecule for myoblast fusion. J Biol Chem 269:14371–14374;1994.PubMedGoogle Scholar
  23. 23.
    Leon SH, Schuffler MD, Kettler M, Rohrmann CA. Chronic intestinal pseudoobstruction as a complication of Duchenne's muscular dystrophy. Gastroenterology 90:455–459;1986.PubMedGoogle Scholar
  24. 24.
    Levine B, Kalman J, Mayer L, Fillit HM, Packer M. Elevated circulating levels of tumour necrosis factor in severe chronic heart failure. N Eng J Med 323:236–241;1990.Google Scholar
  25. 25.
    Riggs T. Cardiomyopathy and pulmonary emboli in terminal Duchenne's muscular dystrophy. Am Heart J 119:690–693;1990.PubMedGoogle Scholar
  26. 26.
    Sander M, Chavoshan B, Harris SA, Iannaccone ST, Stull JT, Thomas GD, Victor RG. Functional muscle ischemia in neuronal nitric oxide synthase-deficient skeletal muscle of children with Duchenne muscular dystrophy. Proc Natl Acad Sci USA 97:13818–13823;2000.CrossRefPubMedGoogle Scholar
  27. 27.
    Schoser BG, Lück G, Blottner D. Partial loss of NADPH-diaphorase/nitric oxide synthase-complex in amyotrophic lateral sclerosis and human type-II myofiber atrophy. Neurosci Lett 231:163–166;1997.CrossRefPubMedGoogle Scholar
  28. 28.
    Straub V, Ratjen F, Amthor H, Voit T, Grasemann H. Airway nitric oxide in Duchenne muscular dystrophy. J Pediatr 141:132–134;2002.CrossRefPubMedGoogle Scholar
  29. 29.
    Thomas GD, Sander M, Lau KS, Huang PL, Stull JT, Victor RG. Impaired metabolic modulation of alpha-adrenergic vasoconstriction in dystrophin-deficient skeletal muscle. Proc Natl Acad Sci USA 95:15090–15095;1998.CrossRefPubMedGoogle Scholar
  30. 30.
    Winlaw DS, Smythe GA, Keogh AM, Schyvens CG, Spratt PM, Macdonald PS. Increased nitric oxide production in heart failure. Lancet 344:373–374;1994.CrossRefPubMedGoogle Scholar
  31. 31.
    Yotsukura M, Miyagawa M, Tsuya T, Ishihawa T, Ishikawa K. Pulmonary hypertension in progressive muscular dystrophy of the Duchenne type. Jpn Circ J 52:321–326;1988.PubMedGoogle Scholar

Copyright information

© National Science Council 2004

Authors and Affiliations

  • Takefumi Kasai
    • 1
  • Kazuhiro Abeyama
    • 2
  • Teruto Hashiguchi
    • 2
  • Hidetoshi Fukunaga
    • 3
  • Mitsuhiro Osame
    • 1
  • Kuro Maruyama
    • 2
  1. 1.Department of Neurology and GeriatricsKagoshima University Graduate School of Medical and Dental SciencesKagoshimaJapan
  2. 2.Department of Laboratory and Vascular MedicineKagoshima University Graduate School of Medical and Dental SciencesJapan
  3. 3.Department of NeurologyNational Minamikyusyu HospitalKagoshimaJapan

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