Functional significance of inducible nitric oxide synthase induction and protein nitration in the thermally injured cutaneous microvasculature.
Increased nitric oxide (NO) production after burn injury is well established. However, there is little information relating to the reactions that occur as a consequence of NO generation under such circumstances. We have investigated the synthesis and function of NO in a rat model of local cutaneous thermal injury. We show that NO levels are elevated from 3 hours after injury with a concomitant increase in protein nitration. A selective inducible nitric oxide synthase (iNOS) inhibitor (1400W) significantly attenuated NO synthesis, protein nitration, and neutrophil accumulation in this model, but had no effect on edema formation. The results also indicate that NO synthesis and protein nitration occurred independently of neutrophil accumulation because these parameters were unaffected by depletion of circulating neutrophils. 3-Chlorotyrosine, a marker of neutrophil/myeloperoxidase-mediated protein damage was significantly increased from 1 hour after burn. Our observations provide evidence for the involvement of reactive species in the inflammatory response after burn. The use of selective iNOS inhibitors may represent a novel approach for the management of human burn injuries.
Rawlingson
Andrew
A
Centre for Cardiovascular Biology and Medicine, King's College London, London, United Kingdom.
Shendi
Khalid
K
Greenacre
Stanley A
SA
England
Timothy G
TG
Jenner
Andrew M
AM
Poston
Robin N
RN
Halliwell
Barry
B
Brain
Susan D
SD
D000818:Animals; D006358:Hot Temperature; D008297:Male; D008833:Microcirculation / Q000502:physiology*; D023421:Models, Animal; D009504:Neutrophils / Q000502:physiology; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II; D009589:Nitrogen Oxides / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000098:blood supply* / Q000293:injuries*
D009566:Nitrates; D009589:Nitrogen Oxides; D011506:Proteins; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat