Gp91ds‐tat, a selective NADPH oxidase peptide inhibitor, increases blood nitric oxide bioavailability in hind limb ischemia and reperfusion (667.7)

Abstract

I/R injury induces cell death and organ dysfunction in part due to a burst of reactive oxygen species that occurs upon the reintroduction of oxygen into the ischemic area, leading to endothelial dysfunction: decreased blood NO and increased hydrogen peroxide (H2O2 ) levels. We’ve previously shown in isolated rat hearts subjected to I/R injury, gp91ds‐tat attenuated cardiac contractile dysfunction and reduced infarct size compared to controls presumably by the inhibition of NADPH oxidase induced superoxide release. Superoxide can quench NO via the formation of peroxynitrite and also be converted to H2O2 in blood. We attempted to confirm this hypothesis using a rat hind limb I/R model that permitted real time measurements of changes in blood NO and H2O2. NO or H2O2 microsensors were inserted into both femoral veins in anesthetized male rats. One limb’s femoral artery/vein is subjected to I(30min)/R(45min) while the other served as a non‐ischemic sham. Preliminary results show blood NO release significantly increased by the end of reperfusion in gp91ds‐tat treated rats (1.2 mg/kg, MW 2452g/mol, n=5) compared to saline treated rats (n=3;p<0.05). The preliminary data suggest that gp91ds‐tat attenuates I/R induced endothelial dysfunction. The results of gp91ds‐tat on blood H2O2 levels are forthcoming.