Inhibition of iNOS attenuates skeletal muscle reperfusion injury in extracellular superoxide dismutase knockout mice

Jong Woong Park, Wen Ning Qi, John Q. Liu, James R. Urbaniak, Rodney J. Folz, Long En Chen

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are closely involved in the mechanism of skeletal muscle ischemia/reperfusion (I/R) injury. This study was designed to determine the effects of inducible nitric oxide synthase (iNOS) inhibitor 1400W on the reperfused cremaster muscle in extracellular superoxide dismutase knockout (EC-SOD-/-) mice. The muscle was exposed to 4.5 h of ischemia, followed by 90 min of reperfusion. Mice received either 3 mg/kg of 1400W or the same amount of phosphate-buered saline (PBS, as a control) subcutaneously at 10 min before the start of reperfusion. 1400W treatment markedly improved the recovery speed of vessel diameter and blood flow in the reperfused cremaster muscle of EC-SOD-/- mice compared to controls. Histological examination showed reduced edema in the interstitial space and muscle fiber, and reduced density of nitrotyrosine (a marker of total peroxinitrite (ONOO-) level) in 1400W-treated muscles compared to controls. Our results suggest that iNOS and ONOO- products are involved in skeletal muscle I/R injury. Reduced I/R injury by using selective inhibition of iNOS perhaps works by limiting cytotoxic ONOO - generation, a reaction product of nitric oxide (NO) and superoxide anion (O2 -). Thus, inhibition of iNOS appears to be a treatment strategy for reducing clinical I/R injury.

Original languageEnglish
Pages (from-to)606-613
Number of pages8
JournalMicrosurgery
Volume25
Issue number8
DOIs
Publication statusPublished - 2005 Dec 15

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Nitric Oxide Synthase Type II
Reperfusion Injury
Knockout Mice
Superoxide Dismutase
Skeletal Muscle
Abdominal Muscles
Muscles
Reperfusion
Reactive Nitrogen Species
Superoxides
Blood Vessels
Reactive Oxygen Species
Edema
Nitric Oxide
Ischemia
Phosphates

ASJC Scopus subject areas

  • Surgery

Cite this

Inhibition of iNOS attenuates skeletal muscle reperfusion injury in extracellular superoxide dismutase knockout mice. / Park, Jong Woong; Qi, Wen Ning; Liu, John Q.; Urbaniak, James R.; Folz, Rodney J.; Chen, Long En.

In: Microsurgery, Vol. 25, No. 8, 15.12.2005, p. 606-613.

Research output: Contribution to journalArticle

Park, Jong Woong ; Qi, Wen Ning ; Liu, John Q. ; Urbaniak, James R. ; Folz, Rodney J. ; Chen, Long En. / Inhibition of iNOS attenuates skeletal muscle reperfusion injury in extracellular superoxide dismutase knockout mice. In: Microsurgery. 2005 ; Vol. 25, No. 8. pp. 606-613.
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