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(Circulation. 2004;110:3349-3354.)
© 2004 American Heart Association, Inc.

Vascular Medicine

Simvastatin Prevents Vascular Hyporeactivity During Inflammation

Johannes Pleiner, MD; Georg Schaller, MD; Friedrich Mittermayer, MD; Stefan Zorn, MS; Claudia Marsik, MD; Stefan Polterauer, MS; Stylianos Kapiotis, MD; Michael Wolzt, MD

From the Department of Clinical Pharmacology (J.P., G.S., F.M., S.Z., C.M., S.P., M.W.), Institute for Medical and Chemical Laboratory Diagnostics (C.M., S.K.), Medical University of Vienna, Vienna, Austria.

Correspondence to Dr Michael Wolzt, Department of Clinical Pharmacology, Allgemeines Krankenhaus Wien, Währinger Gürtel 18-20, A-1090 Vienna, Austria. E-mail michael.wolzt{at}meduniwien.ac.at

Received June 15, 2004; revision received August 18, 2004; accepted September 13, 2004.

Background— There is growing evidence that statins exert anti-inflammatory and antioxidative vascular actions that are independent of lipid lowering. We tested whether hyporeactivity to the endothelium-dependent vasodilator acetylcholine (ACh) and the vasoconstrictor norepinephrine (NE) during acute experimental inflammation could be prevented by simvastatin.

Methods and Results— In a randomized, placebo-controlled, parallel group study, forearm blood flow (FBF) responses to NE, ACh, and the endothelium-independent vasodilator nitroglycerin (NTG) were assessed at baseline, after 4 days of simvastatin 80 mg PO or placebo treatment, and during Escherichia coli endotoxin (lipopolysaccharide [LPS])–induced inflammation in 20 healthy volunteers. Additionally, markers of inflammation and neutrophil oxidative burst were assessed. Simvastatin and placebo had no effect on FBF or oxidative/inflammatory markers. LPS administration decreased the responses of FBF to NE by 43% (P<0.05) and decreased responses to ACh by 48% (P<0.05) but did not decrease FBF responses to NTG. Simvastatin completely preserved responses to NE and to ACh. The LPS-induced increases in neutrophil oxidative burst and plasma tumor necrosis factor- concentrations were mitigated by simvastatin (P<0.05 versus placebo).

Conclusions— This study demonstrates potent vasoprotective properties of high-dose simvastatin during endotoxemia that may be useful for patients with acute systemic inflammation and associated vascular hyporeactivity.

Key Words: inflammation • endothelium • vasoconstriction • statins

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