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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

View larger version (15K): [in a new window]   Figure 1 Expression of myocardial endothelial nitric oxide synthase messenger-ribonucleic acid 18 h following intraperitoneal injection with either saline vehicle (n = 3) or 0.5 mg/kg rosuvastatin (n = 3). Samples were subjected to reverse transcription-polymerase chain reaction and normalized to GAPDH as an internal control. *p < 0.05.

View larger version (15K): [in a new window]   Figure 2 Assessment of nitric oxide (NO) release from thoracic aortic segments of mice injected with either saline vehicle (n = 4) or 0.5 mg/kg rosuvastatin (n = 4) 18 h before harvesting tissue. Rosuvastatin significantly (p < 0.05) augmented vascular NO production via NO synthase. L-NAME = N-G-nitro-L-arginine methyl ester.

View larger version (46K): [in a new window]   Figure 3 Assessment of the effect of varying doses of rosuvastatin administered 18 h before myocardial ischemia and reperfusion in wild-type mice. (A) The areas-at-risk per left ventricle were similar among all groups of mice. (B) The lowest (0.1 mg/kg) and highest (5 mg/kg) doses did not significantly (p = NS) affect the extent of myocardial necrosis. However, intermediate doses (0.5, 1.0, and 2.0 mg/kg) significantly (*p < 0.05) attenuated the degree of myocardial injury following ischemia and reperfusion.

View larger version (48K): [in a new window]   Figure 4 Myocardial necrosis in wild-type mice following injection of either saline vehicle or 0.5 mg/kg rosuvastatin before myocardial ischemia and reperfusion. (A) The areas-at-risk per left ventricle were similar among all groups of mice. (B) Pretreatment with rosuvastatin immediately before ischemia (0 h) or 3 h prior to ischemia did not significantly (p = NS) affect the extent of myocardial necrosis. However, pretreatment as short as 6 h significantly (*p < 0.05) attenuated the extent of myocardial necrosis following ischemia and reperfusion.

View larger version (18K): [in a new window]   Figure 5 The role of endothelial nitric oxide synthase (eNOS) in the attenuation of myocardial ischemia–reperfusion injury following injection with rosuvastatin. Mice deficient in eNOS were administered either saline vehicle (n = 5) or 0.5 mg/kg rosuvastatin (n = 5) 18 h before being subjected to myocardial ischemia and reperfusion. Rosuvastatin failed to significantly (p = NS) alter the extent of myocardial injury in eNOS-deficient mice. AAR = areas-at-risk; LV = left ventricle; NEC = necrosis.