Hypoxia-inducible factor-1 activation and cyclo-oxygenase-2 induction are early reperfusion-independent inflammatory events in hemorrhagic shock.
Hemorrhagic shock (HS) initiates an inflammatory response that includes increased expression of inducible nitric oxide synthase (iNOS) and production of prostaglandins. Induction of iNOS during the ischemic phase of HS may involve the activation of the hypoxia-inducible factor-1 (HIF-1). Increased expression of cyclooxygenase-2 (COX-2) during HS contributes to prostaglandin production. The aim of this study was to determine whether the ischemic phase of HS results in the activation of HIF-1 and the induction of COX-2. The lungs of rats subjected to HS demonstrated a twofold increase in HIF-1 activation (P < 0.01) and a 7.4-fold increase in expression of COX-2 mRNA (P < 0.01) compared with sham controls. The upregulation of iNOS and COX-2 during ischemia are two important early response genes that promote the inflammatory response and may contribute to organ damage through the rapid and exaggerated production of nitric oxide and prostaglandins.
Hierholzer
C
C
Department of Surgery, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Harbrecht
B G
BG
Billiar
T R
TR
Tweardy
D J
DJ
D000818:Animals; D051546:Cyclooxygenase 2; D004268:DNA-Binding Proteins / Q000235:genetics*; D004790:Enzyme Induction / Q000235:genetics; D015870:Gene Expression / Q000502:physiology; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007527:Isoenzymes / Q000235:genetics*; D008168:Lung / Q000098:blood supply* / Q000473:pathology; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology*; D012771:Shock, Hemorrhagic / Q000473:pathology / Q000503:physiopathology*; D018746:Systemic Inflammatory Response Syndrome / Q000473:pathology / Q000503:physiopathology*; D014157:Transcription Factors; D015854:Up-Regulation / Q000235:genetics
D004268:DNA-Binding Proteins; C497444:Hif1a protein, rat; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007527:Isoenzymes; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases