title: Reperfusion injury in skeletal muscle is reduced in inducible nitric oxide synthase knockout mice.
abstract: 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.
authors.affiliation: Orthopaedic Research Laboratory, Duke Univ. Medical Center, Box 3093, Durham, NC 27710, USA.
authors.forename: Wen-Ning
authors.initials: WN
authors.lastname: Qi
authors.forename: Long-En
authors.initials: LE
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Jerry P
authors.initials: JP
authors.lastname: Eu
authors.forename: Anthony V
authors.initials: AV
authors.lastname: Seaber
authors.forename: James R
authors.initials: JR
authors.lastname: Urbaniak
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000473:pathology* / Q000503:physiopathology*; D019001:Nitric Oxide Synthase / Q000172:deficiency*; D052247:Nitric Oxide Synthase Type II; D020127:Recovery of Function / Q000502:physiology; D015427:Reperfusion Injury / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology*; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse