Reperfusion injury in skeletal muscle is reduced in inducible nitric oxide synthase knockout mice.

Published

Journal Article

Inducible nitric oxide synthase (iNOS) participates in many pathological events, and selective inhibition of iNOS has been shown to reduce ischemia-reperfusion (I/R) injury in different tissues. To further confirm its role in this injury process, I/R injury was observed in denervated cremaster muscles of iNOS-deficient (iNOS-/-) and wild-type mice. After 3-h ischemia and 90-min reperfusion, blood flow in reperfused muscle was 80 +/- 8.5% (mean +/- SE) of baseline at 10-min reperfusion and completely returned to the preischemia baseline after 20 min in iNOS-/- mice. In contrast, blood flow was 32 +/- 7.4% at 10 min and increased to 60 +/- 20% of the baseline level at 90 min in wild-type mice (P < 0.001 vs. iNOS-/- mice at all time points). The increased muscle blood flow in iNOS-/- mice was associated with significantly less vasospasm in all three sizes of arterial vessel size categories. The weight ratio to the contralateral muscle not subjected to I/R was greater in wild-type mice (173 +/- 11%) than in iNOS-/- mice (117 +/- 3%; P < 0.01). Inflammation and neutrophil extravasation were also more severe in wild-type mice. Western blot analysis demonstrated an absence of iNOS protein band in iNOS-/- mice and upregulation of iNOS protein expression in wild-type mice. Our results confirm the importance of iNOS in I/R injury. Upregulated iNOS exacerbates I/R injury and appears to be a therapeutic target in protection of tissues against this type of injury.

Full Text

Duke Authors

Cited Authors

  • Qi, W-N; Chen, L-E; Zhang, L; Eu, JP; Seaber, AV; Urbaniak, JR

Published Date

  • October 2004

Published In

Volume / Issue

  • 97 / 4

Start / End Page

  • 1323 - 1328

PubMed ID

  • 15180976

Pubmed Central ID

  • 15180976

International Standard Serial Number (ISSN)

  • 8750-7587

Digital Object Identifier (DOI)

  • 10.1152/japplphysiol.00380.2004

Language

  • eng

Conference Location

  • United States