Direct vascular and cardioprotective effects of rosuvastatin, a new HMG-CoA reductase inhibitor.
OBJECTIVE
We examined the possible effects of a novel 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, rosuvastatin, on endothelial nitric oxide (NO) production and myocardial ischemia-reperfusion injury.


BACKGROUND
Recent studies suggest that HMG-CoA reductase inhibitors promote vascular endothelial function through enhanced endothelial NO production. However, it is unclear whether all statins share this beneficial side effect or whether this effect is limited to the "natural" statins.


METHODS
Wild-type mice (n = 158) were subjected to 30 min of regional myocardial ischemia and 24 h of reperfusion. Mice were treated with various doses of rosuvastatin (0.1, 0.5, 1.0, 2.0, and 5.0 mg/kg) 18 h before myocardial ischemia and reperfusion.


RESULTS
Rosuvastatin significantly increased NO production from the vascular endothelium following acute administration to mice. In addition, rosuvastatin increased myocardial endothelial nitric oxide synthase (eNOS) messenger ribonucleic acid levels. Myocardial necrosis was reduced by approximately 40% with rosuvastatin therapy. Rosuvastatin attenuated myocardial injury when it was administered 6 h, but not 0 h or 3 h, before myocardial ischemia. In additional studies, rosuvastatin did not affect myocardial infarct size in eNOS-deficient mice compared to vehicle-treated eNOS mice.


CONCLUSIONS
These data demonstrate that rosuvastatin increases vascular endothelial NO production and attenuates myocardial necrosis following ischemia and reperfusion in mice.
D000818:Animals; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism*; D005464:Fluorobenzenes / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D006439:Hemodynamics / Q000187:drug effects; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009569:Nitric Oxide / Q000378:metabolism*; D011743:Pyrimidines; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides; D013997:Time Factors
D002316:Cardiotonic Agents; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D009569:Nitric Oxide; D000068718:Rosuvastatin Calcium