title: Nicorandil Protects the Heart from Ischemia/Reperfusion Injury by Attenuating Endoplasmic Reticulum Response-induced Apoptosis Through PI3K/Akt Signaling Pathway.
abstract: OBJECTIVE
  As a vasodilatory drug used to treat angina, nicorandil has been shown to induce an infarct-limiting effect in various experimental animal models of myocardial ischemia-reperfusion (IR). There are multiple mechanisms causing the IR injury, among which, the endoplasmic reticulum (ER) stress and ER stress-initiated apoptosis are implicated to play an important role. However, whether ER stress is involved in nicorandil-induced cardioprotection is unknown.
  
  
  METHODS
  Post-ischemic functional recovery, lactate dehydrogenase (LDH) release and infarct size in perfused rat hearts subjected to global no-flow I/R were measured to analysis the effect of nicorandil and ER stress inducer of tunicamycin as well as phosphatidylinositol 3-kinase (PI3K) inhibitor of wortmannin on the I/R hearts. The I/R hearts tissue were harvested to evaluate apoptosis ratio with TUNEL assay and protein expression with western blot.
  
  
  RESULTS
  We showed that nicorandil ameliorated postischemic contractile recovery, as well as significantly reduced myocardial infarct size at a dose-dependent manner. Furthermore, nicorandil treatment inhibited the IR-induced apoptosis and ER stress. The beneficial effects of nicorandil were blocked by ER stress inducer, tunicamycin and specific phosphatidylinositol 3-kinase (PI3K) inhibitor, wortmannin. CONCOLUSION: We conclude that the cardioprotection of nicorandil was at least in part mediated via inhibition of ER stress-induced apoptotic cell death through PI3K/Akt pathway.
authors.affiliation: Institute of Cardiovascular Diseases, China Three Gorges University, Yichang, Hubei, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wu
authors.forename: Ming
authors.initials: M
authors.lastname: Ye
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.forename: Jiawang
authors.initials: J
authors.lastname: Ding
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.forename: Wusong
authors.initials: W
authors.lastname: Dong
authors.forename: Xinan
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D057775:Ischemic Postconditioning / Q000379:methods; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000378:metabolism; D020108:Nicorandil / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D020011:Protective Agents / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D020011:Protective Agents; D020108:Nicorandil; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt