Acute reduction of myocardial infarct size by a hydroxymethyl glutaryl coenzyme A reductase inhibitor is mediated by endothelial nitric oxide synthase.
In addition to their lipid-lowering properties, statins improve endothelial function by increasing the activity of endothelial nitric oxide synthase (eNOS). It was hypothesized that, by this mechanism, statins protect the myocardium from ischemia/reperfusion injury in normocholesterolemic animals. Rats were pretreated for 1 week with either cerivastatin (0.3 mg/kg/d) or placebo. Anesthetized animals underwent 30 minutes of coronary artery occlusion (CAO) followed by 180 minutes of reperfusion. In a separate set of experiments, the NOS inhibitor l-NAME (15 mg/kg; N -nitro-l-arginine methyl ester) was administered 15 minutes before CAO. Cerivastatin decreased infarct size by 49% (P < 0.05) without reducing plasma cholesterol levels. Cerivastatin increased myocardial eNOS mRNA and NOS activity and by 52% and 58% (P < 0.05), respectively. Cardioprotection and upregulation of eNOS activity evoked by cerivastatin were not observed in rats cotreated with l-NAME. These results show that statins reduce the extent of myocardial necrosis in normocholesterolemic rats after acute ischemia/reperfusion injury by increasing myocardial eNOS activity. Therefore, statins may protect the heart not only by reducing the incidence of ischemic events, but also by limiting cell damage during acute myocardial infarction.
Wolfrum
Sebastian
S
Medical Clinic II , University of Lübeck, Germany.
Grimm
Michael
M
Heidbreder
Marc
M
Dendorfer
Andreas
A
Katus
Hugo A
HA
Liao
James K
JK
Richardt
Gert
G
D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000502:physiology*; D052250:Nitric Oxide Synthase Type III; D051381:Rats; D017208:Rats, Wistar
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat