title: Nicorandil reduces myocardial no-reflow by protection of endothelial function via the activation of KATP channel.
abstract: BACKGROUND
  It has been found that nicorandil can attenuate myocardial no-reflow. However, the exact cause of this beneficial effect has remained unclear. We investigated whether the beneficial effect of nicorandil on myocardial no-reflow could be partly due to its protection against endothelial dysfunction.
  
  
  METHODS
  Ligation area and area of no-reflow were determined echocardiographically and pathologically in sixty-two animals randomized into 7 study groups: 9 controls, 9 nicorandil-treated, 8 glibenclamide (K(ATP) channel blocker)-treated, 10 N(G)-monomethyl-L-arginine (L-NMMA, nonselective nitric oxide synthase antagonist)-treated, 10 nicorandil and glibenclamide-treated, 8 nicorandil and L-NMMA-treated and 8 sham-operated. The acute myocardial infarction and reperfusion model was created with one 3-h occlusion of the left anterior descending coronary artery followed by 2 h of reperfusion. Constitutive nitric oxide synthase (cNOS) activity and inducible nitric oxide synthase (iNOS) activity were also quantified.
  
  
  RESULTS
  Compared with the control group, nicorandil significantly improved ventricular function, increased coronary blood flow volume (P<0.01), decreased area of no-reflow and reduced necrosis area. Nicorandil also increased the cNOS activity and decreased iNOS activity (P<0.05). L-NMMA and glibenclamide abrogated the effects of nicorandil on ventricular function, coronary blood flow volume, area of no-reflow, necrosis area and cNOS activity, but not iNOS activity.
  
  
  CONCLUSIONS
  The beneficial effect of nicorandil on myocardial no-reflow could be due to its protection of endothelial function via the activation of K(ATP) channel.
authors.affiliation: Department of Cardiology, Cardiovascular Institute and Fu-Wai Heart Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Bei Li Shi Road 167, West City District, Beijing, 100037, China.
authors.forename: Jing-Lin
authors.initials: JL
authors.lastname: Zhao
authors.forename: Yue-Jin
authors.initials: YJ
authors.lastname: Yang
authors.forename: Ji-Lin
authors.initials: JL
authors.lastname: Chen
authors.forename: Lian-Ming
authors.initials: LM
authors.lastname: Kang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wu
authors.forename: Run-Lin
authors.initials: RL
authors.lastname: Gao
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005905:Glyburide / Q000494:pharmacology; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D020108:Nicorandil / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000032:analysis; D009929:Organ Size / Q000187:drug effects; D015221:Potassium Channels / Q000378:metabolism*; D013552:Swine; D013556:Swine, Miniature; D015854:Up-Regulation
chemical_list: D000959:Antihypertensive Agents; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; D020108:Nicorandil; D019001:Nitric Oxide Synthase; D005905:Glyburide