Rosuvastatin, a new HMG-CoA reductase inhibitor, protects ischemic reperfused myocardium in normocholesterolemic rats

Document Type

Article

Publication Date

2003

Abstract

The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have been shown to upregulate endothelial nitric oxide synthase in isolated endothelial cells in a manner that is independent of their lipid-lowering effects. Nitric oxide inhibits polymorphonuclear leukocyte (PMN) adherence and attenuates cardiac dysfunction caused by PMNs after ischemia/reperfusion. Therefore, the authors hypothesized that a new statin, rosuvastatin, could attenuate PMN-induced cardiac dysfunction, and examined the effects of rosuvastatin in isolated ischemic (20 min) and reperfused (45 min) rat hearts perfused with PMNs. Rosuvastatin (0.25 or 1.25 mg/kg) given 18 h before ischemia/reperfusion significantly improved left ventricular developed pressure (P < 0.01) and the maximal rate of development of left ventricular developed pressure (+dP/dtmax, P <0.01) compared with ischemia/reperfused hearts obtained from rats given 0.9% NaCl. The time point for the improved cardiac performance caused by rosuvastatin (1.25 mg/kg) was 20 min after reperfusion. In addition, rosuvastatin significantly reduced PMN adherence to the vascular endothelium and subsequent infiltration into the postischemic myocardium (P < 0.01). The nitric oxide synthase inhibitor Nε-nitro-L-arginine methyl ester (50 µmol/l) blocked these cardioprotective effects. These results provide evidence that rosuvastatin significantly attenuates PMN-induced cardiac contractile dysfunction in the isolated perfused rat heart.

Publication Title

Journal of cardiovascular pharmacology

Volume

41

Issue

4

First Page

649

Last Page

656

Comments

This article was published in Journal of cardiovascular pharmacology, Volume 41, Issue 4, Pages 649-656.

The published version is available at http://dx.doi.org/10.1097/00005344-200304000-00019.

Copyright © 2003 LWW, Inc.

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