The mechanism of nitrate-induced preconditioning.
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.
Gori
Tommaso
T
Department of Internal, Cardiovascular and Geriatric Medicine, University of Siena, Siena, Italy. tommaso.gori@utoronto.ca
Di Stolfo
Giuseppe
G
Dragoni
Saverio
S
Lisi
Monica
M
Leone
Maria Cristina
MC
Forconi
Sandro
S
Parker
John D
JD
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
D005609:Free Radicals; D009566:Nitrates; D020030:Nitric Oxide Donors; D009574:Nitro Compounds; D017382:Reactive Oxygen Species; D005996:Nitroglycerin