title: Nicorandil preserves the function of the mitochondrial phosphorylative and oxidative system in an animal model of global ischemia-reperfusion.
abstract: Ischemia followed by reperfusion (IR) negatively affects mitochondrial function. At the level of the oxidative-phosphorylative system, IR inhibits the respiratory complexes and ATP synthase, and increases the passive leak of protons through the inner mitochondrial membrane, uncoupling respiration from phosphorylation, decreasing mitochondrial potential and, consequently, ATP production. Drugs that minimize the mitochondrial damage induced by IR may prove to be clinically effective. In the present work, we analyzed the impact of nicorandil, a mitochondrial ATP-sensitive potassium channel agonist, on mitochondrial dysfunction at the level of the oxidative-phosphorylative system of rat hearts subjected to IR. The decrease in the respiratory control ratio (RCR) induced by IR leads to the conclusion that IR has a negative impact on the activity of the mitochondrial respiratory system, uncoupling oxidation from phosphorylation. This effect is reversed by nicorandil, which increases not only RCR, but also the ADP/O ratio. Regarding respiratory rate, state 3 rate was approximately the same for all the experimental groups, while state 4 rate was lower for the group where IR was induced in the presence of nicorandil. This result is in accordance with the data obtained for the RCR and ADP/O. State 4 rate is most affected by uncoupling, given that it is controlled by proton leak. Mitochondria subjected to IR in the presence of nicorandil have a lower state 4 rate, i.e. they are less uncoupled. From these results we conclude that nicorandil preserves the function of mitochondria subjected to IR in terms of both respiration and phosphorylative capacity.
authors: Serviço de Cardiologia, Hospitais da Universidade de Coimbra, Coimbra, Portugal.
authors: Raquel
authors: R
authors: Carreira
authors: Pedro
authors: P
authors: Monteiro
authors: Lino M
authors: LM
authors: Gonçalves
authors: Luís A
authors: LA
authors: Providência
mesh_terms: D000818:Animals; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D020108:Nicorandil / Q000627:therapeutic use*; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D015221:Potassium Channels / Q000819:agonists; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism*
chemical_list: D015221:Potassium Channels; D020108:Nicorandil