Modulation of tendon healing by nitric oxide

Inflamm Res. 1997 Jan;46(1):19-27. doi: 10.1007/s000110050027.


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 N omega-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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Achilles Tendon / injuries*
  • Achilles Tendon / surgery
  • Animals
  • Biomechanical Phenomena
  • Body Weight / drug effects
  • Enzyme Inhibitors
  • Fluorescent Antibody Technique, Direct
  • Immunohistochemistry
  • Kinetics
  • Male
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide / pharmacology*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Wound Healing / drug effects*


  • Enzyme Inhibitors
  • Nitric Oxide
  • Nitric Oxide Synthase
  • NG-Nitroarginine Methyl Ester