Nitroglycerine causes mitochondrial reactive oxygen species production: In vitro mechanistic insights

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

Research output: Contribution to journalArticle

Abstract

Background: Nitroglycerine (GTN) is an organic nitrate that has been used for more than 100 years. Despite its widespread clinical use, several aspects of the pharmacology of GTN remain elusive. In a recent study, the authors of the present study showed that GTN causes opening of the mitochondrial permeability transition pore (mPTP) and mitochondrial production of reactive oxygen species (ROS). Objective: In the present study, it was tested whether GTN-induced ROS production depends on mitochondrial potassium ATP-dependent channel or mPTP opening, and/or GTN biotransformation. Methods and results: Isolated rat heart mitochondria were incubated with succinate (a substrate for complex II) and GTN, causing immediate ROS production, as manifested by chemiluminescence. This ROS production was prevented by concomitant vitamin C incubation. Conversely, inhibitors of potassium ATP-dependent channels, mPTP opening or of GTN biotransformation did not modify ROS production. Conclusions: GTN triggers mitochondrial ROS production independently of the opening of mitochondrial channels and/or of GTN biotransformation. The present data, coupled with previous evidence published by the same authors that GTN causes opening of mPTPs, provide further evidence on the pharmacology of GTN. It is proposed that GTN causes direct uncoupling of the respiratory chain, which determines ROS production and subsequent mPTP opening. The clinical implications of these findings are also discussed.

Original languageEnglish
Pages (from-to)990-992
Number of pages3
JournalCanadian Journal of Cardiology
Volume23
Issue number12
Publication statusPublished - Oct 2007

Keywords

  • Mitochondria
  • Nitroglycerine
  • Reactive oxygen species

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Gori, T., Daiber, A., Di Stolfo, G., Sicuro, S., Dragoni, S., Lisi, M., Münzel, T., Forconi, S., & Parker, J. D. (2007). Nitroglycerine causes mitochondrial reactive oxygen species production: In vitro mechanistic insights. Canadian Journal of Cardiology, 23(12), 990-992.