title: Neither nitrite nor nitric oxide mediate toxic effects of nitroglycerin on mitochondria.
abstract: It is commonly accepted that the major effect of nitroglycerin (NG) is realized through the release of nitric oxide (NO) catalyzed by aldehyde dehydrogenase-2 (ALDH2). In addition, it has been shown that NG inhibits mitochondrial respiration. The aim of this study was to clarify whether NG-mediated inhibition of mitochondrial respiration is mediated by NO. In rat liver mitochondria, NG inhibited complex-I-dependent respiration and induced reactive oxygen species (ROS) production, preferentially at complex I. Both effects were insensitive to chloral hydrate, an ALDH2 inhibitor. Nitrite, an NG intermediate, had no influence on either mitochondrial respiration or the production of ROS. NO inhibited preferentially complex I but did not elevate ROS production. Hemoglobin, an NO scavenger, and blue light had contrary effects on mitochondria inhibited by NO or NG. In summary, our data suggest that although NG induces vasodilatation via NO release, it causes mitochondrial dysfunction via an NO-independent pathway.
authors.affiliation: Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Austrian Workers' Compensation Board Research Center, A-1200 Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Dungel
authors.forename: Susanne
authors.initials: S
authors.lastname: Haindl
authors.forename: Tricia
authors.initials: T
authors.lastname: Behling
authors.forename: Bernd
authors.initials: B
authors.lastname: Mayer
authors.forename: Heinz
authors.initials: H
authors.lastname: Redl
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Kozlov
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000818:Animals; D002697:Chloral Hydrate / Q000494:pharmacology; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006454:Hemoglobins / Q000378:metabolism; D008027:Light; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000201:enzymology / Q000528:radiation effects; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology; D009573:Nitrites / Q000378:metabolism / Q000494:pharmacology; D005996:Nitroglycerin / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects
chemical_list: D004791:Enzyme Inhibitors; D006454:Hemoglobins; D024101:Mitochondrial Proteins; D009573:Nitrites; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D002697:Chloral Hydrate; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; C505112:Aldh2 protein, rat; D042967:Electron Transport Complex I; D005996:Nitroglycerin