EXPERIMENTAL STUDY
Direct vascular and cardioprotective effects of rosuvastatin, a new HMG-CoA reductase inhibitor
Steven P. Jones, PhD*,
Michael F. Gibson, MD ,
David M. Rimmer, III, MD,
Terrie M. Gibson, MD ,
Brent R. Sharp, BS* and
David J. Lefer, PhD*,*
* Department of Molecular and Cellular Physiology, Louisiana State University, Health Sciences Center, Shreveport, Louisiana, USA
Department of Surgery, Louisiana State University, Health Sciences Center, Shreveport, Louisiana, USA
Department of Medicine, Division of Cardiology, Louisiana State University, Health Sciences Center, Shreveport, Louisiana, USA
Manuscript received June 27, 2001;
revised manuscript received April 12, 2002,
accepted June 12, 2002.
* Reprint requests and correspondence: David J. Lefer, PhD, Department of Molecular and Cellular Physiology, LSU Health Sciences Center, 1501 Kings Highway, Shreveport, Louisiana 71130, USA.
dlefer{at}lsuhsc.edu
OBJECTIVES: 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.
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Abbreviations and Acronyms
| | AAR | | areas-at-risk | | eNOS | | endothelial nitric oxide synthase | | HMG-CoA | | 3-hydroxy-3-methylglutaryl coenzyme A | | LAD | | left anterior descending coronary artery | | L-NAME | | N-G-nitro-L-arginine methyl ester | | MI | | myocardial infarction | | mRNA | | messenger ribonucleic acid | | NEC | | necrosis | | NO | | nitric oxide | | RT-PCR | | reverse transcription-polymerase chain reaction |
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