Modulation of tendon healing by nitric oxide

G. A.C. Murrell, C. Szabo, J. A. Hannafin, D. Jang, M. M. Dolan, X. H. Deng, D. F. Murrell, R. F. Warren

Research output: Contribution to journalArticlepeer-review

117 Scopus citations


Nitric oxide (NO.) is a small, diffusible free radical that is generated from L-arginine by a family of enzymes, collectively termed the nitric oxide synthases. We investigated the role of NO. in tendon healing. NO. synthase activity and immunoreactivity was absent in un-injured rat Achilles tendon. After surgical division there was a five-fold increase in NO. synthase activity and immunoreactivity within the healing tendon at day 7, with a return to near baseline levels at day 14. Inhibition of NO. synthase activity with oral administration of Nω-nitro-L-arginine methyl ester (L-NAME) resulted in a significant reduction in cross-sectional area (30% at day 7, p < 0.01, 50% at day 15, p < 0.001) and failure load (24% at day 7, p < 0.01) of the healing Achilles tendon constructs. Rats fed the same regimen of the enantiomer of L-NAME, (D-NAME) had normal tendon healing. These results indicate that nitric oxide synthase is induced during tendon healing and inhibition of nitric oxide synthase inhibits this tendon healing.

Original languageEnglish (US)
Pages (from-to)19-27
Number of pages9
JournalInflammation Research
Issue number1
StatePublished - 1997
Externally publishedYes


  • Free radical
  • Nitric oxide
  • Nitric oxide synthase
  • Tendon healing
  • Wound healing

ASJC Scopus subject areas

  • Immunology
  • Pharmacology


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