Modulation of tendon healing by nitric oxide.
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.
Murrell
G A
GA
Laboratory for Soft Tissue Research, Cornell University Medical College, Hospital for Special Surgery, New York, NY 10021, USA.
Szabo
C
C
Hannafin
J A
JA
Jang
D
D
Dolan
M M
MM
Deng
X H
XH
Murrell
D F
DF
Warren
R F
RF
D000125:Achilles Tendon / Q000293:injuries* / Q000601:surgery; D000818:Animals; D001696:Biomechanical Phenomena; D001835:Body Weight / Q000187:drug effects; D004791:Enzyme Inhibitors; D019085:Fluorescent Antibody Technique, Direct; D007150:Immunohistochemistry; D007700:Kinetics; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014945:Wound Healing / Q000187:drug effects*
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester