title: Simvastatin reduces myocardial infarct size via increased nitric oxide production in normocholesterolemic rabbits.
abstract: OBJECTIVE
  Statins have been reported to be protective against myocardial infarction (MI). Moreover, statin drugs upregulate nitric oxide (NO) in coronary artery independent of lipid-lowering effects. However their precise mechanism for MI-protection is unclear. We investigated the effect of lipophilic statin administration in a normocholesterolemic rabbit MI model.
  
  
  METHODS
  Nω-nitro-L-arginine methylester (L-NAME, 10 mg/kg) or vehicle alone was intravenously administered 20 min before inducing ischemia, followed by intravenous administration of simvastatin (5 mg/kg) or saline 10 min before ischemia. Rabbits then underwent 30 min of coronary occlusion followed by 48 h of reperfusion. The at-risk and infarct areas were calculated as a percentage of the total left ventricular slice area.
  
  
  RESULTS
  Determination of infarct size revealed that pre-ischemic treatment with simvastatin reduced infarct size (30.5 ± 4%) in comparison to controls (45.0 ± 3%) (P < 0.05). This infarct size-reducing effect of simvastatin could be completely abrogated by pretreatment with L-NAME (42.0 ± 4%).
  
  
  CONCLUSIONS
  Pre-ischemic treatment with simvastatin reduces MI size via NO production. Simvastatin could be a useful drug for coronary artery disease patients without dyslipidemia as it has direct protective effects.
authors.affiliation: Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Narentuoya
authors.initials: N
authors.lastname: Bao
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ushikoshi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Shinji
authors.initials: S
authors.lastname: Yasuda
authors.forename: Itta
authors.initials: I
authors.lastname: Kawamura
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Iwasa
authors.forename: Takahiko
authors.initials: T
authors.lastname: Yamaki
authors.forename: Shohei
authors.initials: S
authors.lastname: Sumi
authors.forename: Kenshi
authors.initials: K
authors.lastname: Nagashima
authors.forename: Takuma
authors.initials: T
authors.lastname: Aoyama
authors.forename: Masanori
authors.initials: M
authors.lastname: Kawasaki
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nishigaki
authors.forename: Genzou
authors.initials: G
authors.lastname: Takemura
authors.forename: Shinya
authors.initials: S
authors.lastname: Minatoguchi
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000097:blood; D003331:Coronary Vessels / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006321:Heart / Q000033:anatomy & histology; D006439:Hemodynamics / Q000187:drug effects; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D009929:Organ Size / Q000187:drug effects; D011817:Rabbits; D019821:Simvastatin / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D004791:Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009569:Nitric Oxide; D002784:Cholesterol; D019821:Simvastatin; D019331:NG-Nitroarginine Methyl Ester