title: The mechanism of nitrate-induced preconditioning.
abstract: Nitroglycerin (GTN) has been shown, in both human and animal studies, to induce a protective phenotype that limits tissue damage after ischemia and reperfusion. This phenomenon is similar to ischemic preconditioning, and several reports suggest that also the molecular pathways involved in this protective effect of nitrates are the same that determine ischemic preconditioning. Our group conducted a series of studies aimed at investigating, using a human model of endothelial IR injury, the mechanism of nitrate-induced preconditioning and particularly the role of reactive oxygen species formation and of the opening of mitochondrial permeability transition pores. Our data demonstrate that GTN protects the endothelium against postischemic endothelial dysfunction in a mechanism that is mediated by oxygen free radical release and opening of mitochondrial permeability transition pores. In contrast, the protective effect of pentaerithrityl tetranitrate appears to be independent of these mechanisms, and it seems to be mediated by induction of antioxidant genes. Finally, isosorbide mononitrate seems to be devoid of a significant protective effect. These data are summarized and discussed in the present paper.
authors.affiliation: Department of Internal, Cardiovascular and Geriatric Medicine, University of Siena, Siena, Italy. tommaso.gori@utoronto.ca
authors.forename: Tommaso
authors.initials: T
authors.lastname: Gori
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Stolfo
authors.forename: Saverio
authors.initials: S
authors.lastname: Dragoni
authors.forename: Monica
authors.initials: M
authors.lastname: Lisi
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Leone
authors.forename: Sandro
authors.initials: S
authors.lastname: Forconi
authors.forename: John D
authors.initials: JD
authors.lastname: Parker
mesh_terms: D004730:Endothelium, Vascular / Q000473:pathology; D004867:Equipment Design; D005609:Free Radicals; D006801:Humans; D019194:Ischemic Preconditioning / Q000379:methods*; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D009566:Nitrates / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009574:Nitro Compounds / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology*; D010539:Permeability; D017382:Reactive Oxygen Species; D015427:Reperfusion Injury
chemical_list: D005609:Free Radicals; D009566:Nitrates; D020030:Nitric Oxide Donors; D009574:Nitro Compounds; D017382:Reactive Oxygen Species; D005996:Nitroglycerin