Nicorandil improves post-ischemic myocardial dysfunction in association with opening the mitochondrial K(ATP) channels and decreasing hydroxyl radicals in isolated rat hearts.
BACKGROUND
Nicorandil has been reported to induce cardioprotection by opening the mitochondrial K(ATP) channels. However, whether nicorandil affects reactive oxygen species is unclear.


RESULTS
The hearts of male Sprague-Dawley rats were excised and perfused on a Langendorff apparatus with Krebs-Henseleit solution with a gas mixture of 95% O(2) and 5% CO(2). 1 mmol/L of nicorandil was given 10 min before ischemia. Left ventricular developed pressure (LVDP, mmHg), +/-dP/dt (mmHg/s) and coronary flow (ml/min) were continuously monitored. All hearts were perfused for a total of 120 min consisting of a 30 min pre-ischemic period, followed by a 30 min global ischemia and 60 min reperfusion with and without 5-hydroxydecanoic acid sodium salt (5-HD), a mitochondrial K(ATP) channel blocker. The concentrations of 2,3-dihydroxybenzoic acid (2,3-DHBA), an indicator of hydroxyl radicals, in the perfusate during reperfusion period were also measured. Nicorandil significantly improved LVDP and +/-dP/dt, and increased coronary flow during reperfusion. Pretreatment with 5-HD abolished the improvement of LVDP and +/-dP/dt, and the increase in coronary flow induced by nicorandil. Nicorandil significantly attenuated the concentrations of 2,3-DHBA during reperfusion, which were restored by 5-HD.


CONCLUSIONS
Nicorandil is protective against post-ischemic left ventricular dysfunction in association with opening the mitochondrial K(ATP) channels, decreasing hydroxyl radicals and increasing coronary flow in the isolated rat heart.
Lu
Chuanjiang
C
Second Department of Internal Medicine, Gifu University School of Medicine.
Minatoguchi
Shinya
S
Arai
Masazumi
M
Wang
Ningyuan
N
Chen
Xue-Hai
XH
Bao
Narentuoya
N
Kawamura
Itta
I
Yasuda
Shinji
S
Kobayashi
Hiroyuki
H
Wu
Der-Jinn
DJ
Takemura
Genzou
G
Fujiwara
Hisayoshi
H
D000818:Animals; D006352:Heart Ventricles / Q000187:drug effects; D062385:Hydroxybenzoates; D017665:Hydroxyl Radical / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy; D009206:Myocardium / Q000378:metabolism*; D020108:Nicorandil / Q000494:pharmacology* / Q000627:therapeutic use; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014665:Vasodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use
D062385:Hydroxybenzoates; D015221:Potassium Channels; D014665:Vasodilator Agents; C117780:mitochondrial K(ATP) channel; D020108:Nicorandil; D017665:Hydroxyl Radical; C009135:2,3-dihydroxybenzoic acid