Nicorandil protects cardiac mitochondria against permeability transition induced by ischemia-reperfusion.
Ischemia followed by reperfusion is known to negatively affect mitochondrial function by inducing a deleterious condition termed mitochondrial permeability transition. Mitochondrial permeability transition is triggered by oxidative stress, which occurs in mitochondria during ischemia-reperfusion as a result of lower antioxidant defenses and increased oxidant production. Permeability transition causes mitochondrial dysfunction and can ultimately lead to cell death. A drug able to minimize mitochondrial damage induced by ischemia-reperfusion may prove to be clinically effective. We aimed to analyze the effects of nicorandil, an ATP-sensitive potassium channel agonist and vasodilator, on mitochondrial function of rat hearts and cardiac HL-1 cells submitted to ischemia-reperfusion. Nicorandil decreased mitochondrial swelling and calcium uptake. It also decreased reactive oxygen species formation and thiobarbituric acid reactive substances levels, a lipid peroxidation biomarker. We thus confirm previous reports that nicorandil inhibits mitochondrial permeability transition and demonstrate that nicorandil inhibits this process by preventing oxidative damage and mitochondrial calcium overload induced by ischemia-reperfusion, resulting in improved cardiomyocyte viability. These results may explain the good clinical results obtained when using nicorandil in the treatment of ischemic heart disease.
Carreira
Raquel S
RS
Basic Research Unit in Cardiology, Cardiology Department, Coimbra University Hospital, Azinhaga de Santa Comba, Celas, 3000-548, Coimbra, Portugal. raquelsc@ci.uc.pt
Monteiro
Pedro
P
Kowaltowski
Alicia J
AJ
Gonçalves
Lino M
LM
Providência
Luís A
LA
D000818:Animals; D002316:Cardiotonic Agents / Q000008:administration & dosage*; D002463:Cell Membrane Permeability / Q000187:drug effects* / Q000528:radiation effects; D002478:Cells, Cultured; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D020108:Nicorandil / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar
D002316:Cardiotonic Agents; D020108:Nicorandil