Simvastatin reduces myocardial infarct size via increased nitric oxide production in normocholesterolemic rabbits.
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.
Bao
Narentuoya
N
Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan.
Ushikoshi
Hiroaki
H
Kobayashi
Hiroyuki
H
Yasuda
Shinji
S
Kawamura
Itta
I
Iwasa
Masamitsu
M
Yamaki
Takahiko
T
Sumi
Shohei
S
Nagashima
Kenshi
K
Aoyama
Takuma
T
Kawasaki
Masanori
M
Nishigaki
Kazuhiko
K
Takemura
Genzou
G
Minatoguchi
Shinya
S
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
D004791:Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009569:Nitric Oxide; D002784:Cholesterol; D019821:Simvastatin; D019331:NG-Nitroarginine Methyl Ester