Nitroglycerin protects the endothelium from ischaemia and reperfusion: Human mechanistic insight

Tommaso Gori, Giuseppe Di Stolfo, Silvia Sicuro, Saverio Dragoni, Monica Lisi, Sandro Forconi, John D. Parker

Research output: Contribution to journalArticle

Abstract

Aims: Nitroglycerin (GTN) modulates tissue damage induced by ischaemia and reperfusion (IR) in a mechanism that is similar to ischaemic preconditioning. We set out to study, using a human model of endothelial IR injury, whether GTN-induced endothelial preconditioning is mediated by reactive oxygen species (ROS) formation and/or opening of mitochondrial permeability transition pores (mPTP). Methods: In two double-blind, randomized, parallel studies, a total of 66 volunteers underwent measurement of radial artery endothelium-dependent, flow-mediated dilation (FMD) before and after local IR. Subjects were treated, 24 h before IR, with different drugs in order to test the mechanism of GTN-induced endothelial protection. Results: Transdermal GTN (0.6 mg h -1 for 2 h, administered 24 h before IR) significantly reduced the impairment of FMD caused by IR (placebo group: FMD after IR, 1.3 ± 0.8%; GTN group: FMD after IR, 5.3 ± 0.9%, P <0.01 compared with placebo). This protective effect was lost when vitamin C (2 g i.v. at the time of GTN administration) or ciclosporin (an inhibitor of mPTP, 100 mg 2 h prior to GTN administration) were coadministered (FMD after IR: vit C + GTN group, 2.1 ± 1.0%; ciclosporin + GTN group, 1.7 ± 0.8%; both P <0.05 compared with GTN alone). Conclusions: We demonstrate that GTN protects the endothelium against IR-induced endothelial dysfunction, in an effect similar to delayed ischaemic preconditioning. Using a human model, we provide evidence supporting the concept that this protective effect is mediated by ROS release and mPTP opening upon GTN administration.

Original languageEnglish
Pages (from-to)145-150
Number of pages6
JournalBritish Journal of Clinical Pharmacology
Volume64
Issue number2
DOIs
Publication statusPublished - Aug 2007

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Keywords

  • Endothelium
  • Ischaemia
  • Reperfusion

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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