title: Nicorandil improves post-ischemic myocardial dysfunction in association with opening the mitochondrial K(ATP) channels and decreasing hydroxyl radicals in isolated rat hearts.
abstract: 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.
authors.affiliation: Second Department of Internal Medicine, Gifu University School of Medicine.
authors.forename: Chuanjiang
authors.initials: C
authors.lastname: Lu
authors.forename: Shinya
authors.initials: S
authors.lastname: Minatoguchi
authors.forename: Masazumi
authors.initials: M
authors.lastname: Arai
authors.forename: Ningyuan
authors.initials: N
authors.lastname: Wang
authors.forename: Xue-Hai
authors.initials: XH
authors.lastname: Chen
authors.forename: Narentuoya
authors.initials: N
authors.lastname: Bao
authors.forename: Itta
authors.initials: I
authors.lastname: Kawamura
authors.forename: Shinji
authors.initials: S
authors.lastname: Yasuda
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Der-Jinn
authors.initials: DJ
authors.lastname: Wu
authors.forename: Genzou
authors.initials: G
authors.lastname: Takemura
authors.forename: Hisayoshi
authors.initials: H
authors.lastname: Fujiwara
mesh_terms: 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
chemical_list: D062385:Hydroxybenzoates; D015221:Potassium Channels; D014665:Vasodilator Agents; C117780:mitochondrial K(ATP) channel; D020108:Nicorandil; D017665:Hydroxyl Radical; C009135:2,3-dihydroxybenzoic acid