Hemorrhage and renal ischemia-reperfusion upregulates the epidermal growthfactor receptor in rabbit duodenum

To study the role of EGF-R in small intestinal adaptation to hemorrhage and I/R, anesthetized rabbits were implanted aseptically with arterial and ven ous catheters and bilateral renal artery Doppler flow probes and silastic o ccluders and allowed to recover. Rabbits were then randomly assigned to one of six groups: time control; hemorrhage (22.5 mL/kg) and 2.5 hours of rena l occlusion (hemorrhage plus I/R); hemorrhage plus I/R and 2:1 LRS resuscit ation; hemorrhage plus I/R and 3:1 LRS resuscitation; hemorrhage alone; or I/R alone. Rabbits were killed 48 hours after hemorrhage, and a section of duodenum was collected for analysis. Hemorrhage plus I/R induced a 2.5-fold increase in EGF-R tyrosine kinase activity compared with that found in the control group (P < .05), and this effect was not modified by either LRS re suscitation regimen. This increased activity was associated with similar in creases in EGF-R protein concentrations and approximately a 50% increase in EGF-R messenger (m)RNA levels compared with levels found in the control gr oup. Further analysis of possible regulatory mechanisms for the increased E GF-R expression after hemorrhage plus I/R detected higher levels of EGF-R p hosphorylation compared with those found in the control group but no signif icant increases in transforming growth factor-alpha mRNA levels. These data , coupled with a significant increase in duodenal thiobarbituric acid-react ive substance concentrations from rabbits in the hemorrhage plus I/R group, support the hypothesis that tyrosine kinase signal transduction pathways i nvolving the EGF-R are activated in the small intestine after hemorrhage, r enal I/R, or both, and this process may be mediated, at least in part, by o xidant stress.