Excessive nitric oxide impairs wound collagen accumulation

Julie E. Park, Morton J. Abrams, Philip A. Efron, Adrian Barbul

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)487-492
Number of pages6
JournalJournal of Surgical Research
Issue number1
StatePublished - Jul 2013
Externally publishedYes


  • Collagen synthesis
  • Inflammation
  • Nitric oxide
  • Wound healing

ASJC Scopus subject areas

  • Surgery


Dive into the research topics of 'Excessive nitric oxide impairs wound collagen accumulation'. Together they form a unique fingerprint.

Cite this