The effect of hyperbaric oxygen on nitric oxide synthase and vascular endothelial growth factor expression in ischemia reperfusion injury

Abstract

Abstract Introduction: Previous work demonstrates that hyperbaric oxygen (HBO) decreases ischemia-reperfusion (IR) injury by blocking CD18 polarization thus inhibiting neutrophil adhesion. The effects of HBO are via a nitric oxide (NO) mechanism which is nitric oxide synthase (NOS) dependent. Recent studies show NOS activity to be stimulated by vascular endothelial growth factor (VEGF). This study was performed to determine whether HBO causes upregulation of NOS isoforms and/or VEGF. Methods: A gracilis flap was raised in 4 groups of Wistar rats: SHAM, SHAM-HBO treated with 100% oxygen at 2.5 ATA for 90 minutes, IR (4 hrs of ischemia) and IR-HBO (4 hrs ischemia + HBO during the last 90 min. of ischemia). After 30 min. reperfusion, samples were harvested from the gracilis muscle, rectus femoris muscle, aorta and pulmonary vessels. Rt-PCR was performed to detect iNOS, eNOS, nNOS and VEGF mRNA. Results: There was no significant difference in mRNA expression of the NOS isoforms between treatment groups or tissues. Expression of VEGF mRNA in gracilis muscle of the IR-HBO group was increased 156% vs SHAM and 82% vs IR (P Conclusions: HBO significantly increases VEGF expression but does not upregulate NOS. Since it is known that HBO’s effect on IR-induced PMN CD18 polarization is NOS dependent, we are currently studying whether HBO increases NOS activity to further elucidate the role of VEGF in this pathway.