title: Pravastatin reduces myocardial infarct size via increasing protein kinase C-dependent nitric oxide, decreasing oxyradicals and opening the mitochondrial adenosine triphosphate-sensitive potassium channels in rabbits.
abstract: BACKGROUND
  Statins reportedly protect against myocardial infarction, but the precise mechanism is unclear.
  
  
  RESULTS
  Rabbits underwent 30 min of coronary occlusion followed by 48 h of reperfusion. Pravastatin (1 or 5 mg/kg) or saline was intravenously administered 10 min before ischemia. Pravastatin (5 mg/kg) was also administered 10 min before reperfusion. N(omega)-nitro-L-arginine methylester (L-NAME, 10 mg/kg), chelerythrine (5 mg/kg) or 5-hydroxydecanoic acid sodium salt (5-HD, 5 mg/kg) was intravenously administered 10 min before pravastatin injection. The infarct size was determined. The myocardial interstitial levels of 2,5-dihydroxybenzoic acid (DHBA) and nitrogen oxide (NOx), and the intensity of myocardial dihydroethidium staining were measured. Pre-ischemic treatment with pravastatin reduced the infarct size (34+/-5% and 24+/-4%, 1 and 5 mg/kg, respectively), but not pre-reperfusion treatment (42.1+/-3.7%), compared with the control (45+/-3%). This effect was blocked by L-NAME (42.6+/-4%), chelerythrine (50.9+/-3%) and 5-HD (52.7+/-2%). Pre-ischemic treatment with pravastatin increased myocardial NOx levels, and attenuated both the 2,5-DHBA level and the intensity of dihydroethidium staining during reperfusion. Chelerythrine abolished the increase in NOx levels by pravastatin.
  
  
  CONCLUSIONS
  Pre-ischemic treatment with pravastatin reduces the myocardial infarct size via protein kinase C-dependent nitric oxide production, decreasing hydroxyl radicals and superoxide, and opening the mitochondrial adenosine triphosphate-sensitive potassium channels.
authors: Second Department of Internal Medicine, Gifu University School of Medicine, Gifu, Japan.
authors: Narentuoya
authors: N
authors: Bao
authors: Shinya
authors: S
authors: Minatoguchi
authors: Hiroyuki
authors: H
authors: Kobayashi
authors: Shinji
authors: S
authors: Yasuda
authors: Itta
authors: I
authors: Kawamura
authors: Masamitsu
authors: M
authors: Iwasa
authors: Takahiko
authors: T
authors: Yamaki
authors: Syohei
authors: S
authors: Sumi
authors: Yu
authors: Y
authors: Misao
authors: Masazumi
authors: M
authors: Arai
authors: Kazuhiko
authors: K
authors: Nishigaki
authors: Genzou
authors: G
authors: Takemura
authors: Takako
authors: T
authors: Fujiwara
authors: Hisayoshi
authors: H
authors: Fujiwara
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods; D054086:KATP Channels / Q000378:metabolism*; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism*; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control*; D009569:Nitric Oxide / Q000378:metabolism*; D017035:Pravastatin / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D054086:KATP Channels; D017382:Reactive Oxygen Species; D013481:Superoxides; D009569:Nitric Oxide; D011493:Protein Kinase C; D017035:Pravastatin