Nicorandil preserves mitochondrial function during ischemia in perfused rat heart.
A possible mechanism for the action of nicorandil on the improvement of energy metabolism of ischemic/reperfused hearts was examined. Perfused rat hearts were subjected to 35-min ischemia/60-min reperfusion. The heart was treated with nicorandil at concentrations of 10 to 100 microM for the last 30-min of pre-ischemia. Nicorandil preserved the mitochondrial oxygen consumption rate during ischemia and attenuated the decrease in mitochondrial function during reperfusion in association with the enhanced post-ischemic recovery of the left ventricular developed pressure. To assess the direct effect on mitochondria, myocardial saponin-skinned bundles were incubated under hypoxic conditions in vitro. Hypoxia-induced decrease in the mitochondrial oxygen consumption rate was attenuated by treatment of the bundles with 100 microM nicorandil. This attenuation was abolished by the combined treatment with the K(ATP) channel blocker, 5-hydroxydecanoate (5-HD). These results suggest that nicorandil is capable of attenuating ischemia/reperfusion injury of isolated perfused hearts through preservation of mitochondrial function during ischemia.
Iwai
Takeshi
T
Department of Pharmacology, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
Tanonaka
Kouichi
K
Motegi
Kanataka
K
Inoue
Rie
R
Kasahara
Sayaka
S
Takeo
Satoshi
S
D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology*; D015687:Cell Hypoxia; D003574:Cytochrome c Group / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism; D017202:Myocardial Ischemia / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D020108:Nicorandil / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D016277:Ventricular Function, Left / Q000187:drug effects
D002317:Cardiovascular Agents; D003574:Cytochrome c Group; D020108:Nicorandil