Inhibition of iNOS attenuates skeletal muscle reperfusion injury in extracellular superoxide dismutase knockout mice
✍ Scribed by Jong Woong Park; Wen-Ning Qi; John Q. Liu; James R. Urbaniak; Rodney J. Folz; Long-En Chen
- Publisher
- John Wiley and Sons
- Year
- 2005
- Tongue
- English
- Weight
- 244 KB
- Volume
- 25
- Category
- Article
- ISSN
- 0738-1085
No coin nor oath required. For personal study only.
✦ Synopsis
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‐buffered 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 (O~2~^−^). Thus, inhibition of iNOS appears to be a treatment strategy for reducing clinical I/R injury. © 2005 Wiley‐Liss, Inc. Microsurgery 25:606–613, 2005.