Rosuvastatin, a new HMG-CoA reductase inhibitor, protects ischemic reperfused myocardium in normocholesterolemic rats.
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/dt(max), 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 N omega-nitro-l-arginine methyl ester (50 micromol/l) blocked these cardioprotective effects. These results provide evidence that rosuvastatin significantly attenuates PMN-induced cardiac contractile dysfunction in the isolated perfused rat heart.
Ikeda
Yasuhiko
Y
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA. yasuhiko@hama-med.ac.jp
Young
Lindon H
LH
Lefer
Allan M
AM
D000818:Animals; D002784:Cholesterol / Q000097:blood*; D005464:Fluorobenzenes / Q000494:pharmacology / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects / Q000502:physiology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D066298:In Vitro Techniques; D015428:Myocardial Reperfusion Injury / Q000097:blood / Q000188:drug therapy*; D011743:Pyrimidines; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides
D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium; D002784:Cholesterol