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Excessive nitric oxide impairs wound collagen accumulation

  • Author Footnotes
    1 Present address: Department of Plastic Surgery, University of Chicago, Chicago, Illinois.
    Julie E. Park
    Footnotes
    1 Present address: Department of Plastic Surgery, University of Chicago, Chicago, Illinois.
    Affiliations
    Department of Surgery, Sinai Hospital of Baltimore, Baltimore, Maryland

    Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland
    Search for articles by this author
  • Author Footnotes
    2 Present address: Department of Surgery, Groote Schuur Hospital, University of Cape town, Cape Town, Republic of South Africa.
    Morton J. Abrams
    Footnotes
    2 Present address: Department of Surgery, Groote Schuur Hospital, University of Cape town, Cape Town, Republic of South Africa.
    Affiliations
    Department of Surgery, Sinai Hospital of Baltimore, Baltimore, Maryland

    Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland
    Search for articles by this author
  • Author Footnotes
    3 Present address: Department of Surgery, University of Florida Health Science Center, Gainesville, Florida.
    Philip A. Efron
    Footnotes
    3 Present address: Department of Surgery, University of Florida Health Science Center, Gainesville, Florida.
    Affiliations
    Department of Surgery, Sinai Hospital of Baltimore, Baltimore, Maryland

    Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland
    Search for articles by this author
  • Author Footnotes
    4 Present address: Department of Surgery, University of Medicine and Dentistry of New Jersey, Newark, New Jersey and Johns Hopkins School of Medicine, Englewood, New Jersey.
    ,
    Author Footnotes
    5 Present address: Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland.
    Adrian Barbul
    Correspondence
    Corresponding author. Department of Surgery, University of Medicine and Dentistry of New Jersey, Newark, NJ, and Johns Hopkins School of Medicine, 41 Brownstone Way, apt 109, Englewood, NJ 07631. Tel.: +1 410 274 1188; fax: +1 201 996 2021.
    Footnotes
    4 Present address: Department of Surgery, University of Medicine and Dentistry of New Jersey, Newark, New Jersey and Johns Hopkins School of Medicine, Englewood, New Jersey.
    5 Present address: Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland.
    Affiliations
    Department of Surgery, Sinai Hospital of Baltimore, Baltimore, Maryland

    Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland
    Search for articles by this author
  • Author Footnotes
    1 Present address: Department of Plastic Surgery, University of Chicago, Chicago, Illinois.
    2 Present address: Department of Surgery, Groote Schuur Hospital, University of Cape town, Cape Town, Republic of South Africa.
    3 Present address: Department of Surgery, University of Florida Health Science Center, Gainesville, Florida.
    4 Present address: Department of Surgery, University of Medicine and Dentistry of New Jersey, Newark, New Jersey and Johns Hopkins School of Medicine, Englewood, New Jersey.
    5 Present address: Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Published:December 28, 2012DOI:https://doi.org/10.1016/j.jss.2012.11.056

      Abstract

      Background

      Nitric oxide (NO) plays a major regulatory role in wound collagen synthesis. We hypothesized that this regulatory role is tightly controlled by the levels of NO in the wound environment and that supranormal wound NO generation impairs wound collagen accumulation.

      Materials and methods

      We used the model of turpentine-induced granuloma in male Sprague–Dawley rats as a sterile inflammatory stimulus generating large amounts of NO. In this environment, NO generation increased by 260%, whereas collagen deposition was significantly reduced by 38.5% (729.7 ± 81.5 versus 449.4 ± 76.3 μg hydroxyproline/100 mg sponge, P<0.05). Inhibition of NO synthase activity using 300 mM L-N6-(1-iminoethyl)-lysine, a highly potent and selective inhibitor of inducible NO synthase, significantly reduced NO elevation by 43.3% and increased wound collagen deposition by 37.3% (P<0.05). These effects occurred without any anti-inflammatory effects of L-N6-(1-iminoethyl)-lysine as assessed by the white blood cell counts and levels of interleukins 1 and 6.

      Conclusions

      The data show that high levels of NO within the wound environment significantly reduce wound collagen deposition. Inhibition of NO generation restores collagen levels to normal levels. The regulatory effects of NO on wound collagen appear to be highly correlated with the amount of NO generated.

      Keywords

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