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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Article info
Publication history
Published online: December 28, 2012
Accepted:
November 30,
2012
Received in revised form:
October 19,
2012
Received:
September 14,
2012
Identification
Copyright
© 2013 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
