Pathogenetic role of endothelial nitric oxide synthase uncoupling during lung ischaemia-reperfusion injury

Jan F. Gielis*, Laurent Quirynen, Jacob J. Briede, Ella Roelant, Paul Cos, Paul E. Y. Van Schil

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


OBJECTIVES: Ischaemia-reperfusion injury is a necessary part of organ transplantation and a key determinant of both acute and chronic graft failure. We have assessed the contribution of endothelial nitric oxide synthase (eNOS) and eNOS uncoupling to oxidative and nitrosative stress formation during lung ischaemia-reperfusion injury dependent on ischaemia time.

METHODS: Forty eNOS wild-type mice (eNOS(+/+)) and 40 eNOS knock-out mice (eNOS(-/-)) received either a sham thoracotomy or 60 or 90 min of ischaemia, followed by 0, 1 or 24 h of reperfusion. Lung tissue was analysed with electron spin resonance for NO production and reactive oxygen species content. Protein nitrosation, eNOS and eNOS uncoupling were determined using western blotting. In peripheral blood, arterial blood gases were taken and reactive oxygen species content was determined.

RESULTS: eNOS(+/+) mice had lower reactive oxygen species production in their peripheral circulation but worse blood gas values after 1 h of reperfusion. Lung tissue of eNOS(-/-) mice showed lower reactive oxygen species and NO production and lower protein nitrosation compared with wild-type mice. Longer ischaemia times result in more elaborate oxidative and nitrosative stress dependent on eNOS genotype. Structural eNOS uncoupling was present after 60 min of ischaemia but diminished after 90 min of ischaemia.

CONCLUSIONS: eNOS uncoupling may contribute to lung ischaemia-reperfusion injury and inflammation. This ultimately leads to worse clinical outcome. Stabilizing eNOS may therefore be a new approach to extend pulmonary graft survival.

Original languageEnglish
Pages (from-to)256-263
Number of pages8
JournalEuropean Journal of Cardio-Thoracic Surgery
Issue number2
Publication statusPublished - Aug 2017


  • Ischaemia-reperfusion injury
  • LIRI
  • Oxidative and nitrosative stress
  • ESR


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