• Gourab Datta, Tu V Luong, Barry J Fuller, and Brian R Davidson.
• Division of Surgery and Interventional Science, University College Hospital, London, United Kingdom.
• J. Surg. Res. 2014 Jan 1; 186 (1): 417-28.

Backgroundischemic preconditioning (IPC) protects against liver ischemia-reperfusion (IR) injury. The mechanism involves nitric oxide metabolism but the importance of endothelial nitric oxide synthase (eNOS) has not been established. Heme oxygenase-1 (HO-1) protects against liver IR but it is unclear if this depends on nitric oxide synthase.Materials And MethodsA mouse model of IPC with liver IR using wild-type (WT) and eNOS transgenic knockout (eNOS-/-) mice was developed to study the role of eNOS and its relationship to HO-1. Serum alanine aminotransferase level, liver histopathologic injury scores, and liver microcirculatory blood flow were measured. Western blots measured liver HO-1/2, eNOS, phosphorylated eNOS, inducible nitric oxide synthase, and reverse transcription-polymerase chain reaction (HO-1). A set of 24-h recovery experiments was undertaken on WT mice with measurement of serum alanine aminotransferase level, histologic injury score, and HO-1 by Western blot.ResultsIn WT animals, IPC preceding IR resulted in a reduction in hepatocellular and histologic injury, and improvement in parenchymal perfusion. In contrast, IPC in the eNOS-/- model did not protect the animals from IR injury. There was no difference between the eNOS and phosphorylated eNOS expression in all the WT groups. HO-1 protein was not detected in the nonrecovery groups but HO-1 messenger RNA was detected in all groups. In WT recovery experiments, IPC was protective against IR injury. HO-1 protein was detected in the IPC + IR and IR only groups but not in the sham group.ConclusionsThis study developed and used an eNOS-/- model to demonstrate that eNOS mediates protection against liver IR injury by IPC. The eNOS expression and activity and HO-1 expression are increased independently in liver IPC and IR, with HO-1 expression increased in the later stages of IPC and IR.Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

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