Direct vascular and cardioprotective effects of rosuvastatin, a new HMG-CoA reductase inhibitor

• Published in: Journal of the American College of Cardiology Vol. 40; no. 6; pp. 1172 - 1178
• Main Authors: Jones, Steven P, Gibson, Michael F, Rimmer, David M, Gibson, Terrie M, Sharp, Brent R, Lefer, David J
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 18.09.2002; Elsevier Science; Elsevier Limited
• Subjects: Animals; Biological and medical sciences; Cardiology; Cardiotonic Agents - administration & dosage; Cardiotonic Agents - pharmacology; Cardiotonic Agents - therapeutic use; Cardiovascular system; Cholesterol; Disease Models, Animal; Dose-Response Relationship, Drug; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Fluorobenzenes - administration & dosage; Fluorobenzenes - pharmacology; Fluorobenzenes - therapeutic use; Heart attacks; Hemodynamics - drug effects; Hydroxymethylglutaryl-CoA Reductase Inhibitors - administration & dosage; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Kinases; Male; Medical sciences; Mice; Mice, Inbred C57BL; Miscellaneous; Myocardial Reperfusion Injury - prevention & control; Nitric oxide; Nitric Oxide - metabolism; Pharmacology. Drug treatments; Pyrimidines; Rosuvastatin Calcium; Statins; Sulfonamides; Time Factors; NO; AAR; eNOS; l-NAME; RT-PCR; HMG-CoA; mRNA; MI; NEC; LAD; Infarct; Cardiovascular disease; Rosuvastatin; Myocardial disease; Vascular disease; Prevention; Reperfusion; Ischemia; Mechanism of action; Enzyme; Treatment efficiency; Rodentia; Enzyme inhibitor; Statin derivative; Coronary heart disease; Endothelium; Vertebrata; Chemotherapy; Mammalia; Treatment; Mouse; Animal; Nitric oxide; Myocardium; Hydroxymethylglutaryl-CoA reductase; Oxidoreductases
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/S0735-1097(02)02115-0

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. 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. 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. 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. These data demonstrate that rosuvastatin increases vascular endothelial NO production and attenuates myocardial necrosis following ischemia and reperfusion in mice.