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 inc reased expression of inducible nitric oxide synthase (iNOS) and production of prostaglandins. Induction of iNOS during the ischemic phase of HS may in volve the activation of the hypoxia-inducible factor-1 (HLF-1). Increased e xpression of cyclooxygenase-2 (COX-2) during HS contributes to prostaglandi n production. The aim of this study was to determine whether the ischemic p hase of HS results in the activation of HIF-1 and the induction of COX-2. T he lungs of rats subjected to I-IS 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 inf lammatory response and may contribute to organ damage through the rapid and exaggerated production of nitric oxide and prostaglandins.