Simvastatin prevents vascular hyporeactivity during inflammation

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 experimenta...

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Published in:Circulation (New York, N.Y.) N.Y.), 2004-11, Vol.110 (21), p.3349-3354
Main Authors: Pleiner, Johannes, Schaller, Georg, Mittermayer, Friedrich, Zorn, Stefan, Marsik, Claudia, Polterauer, Stefan, Kapiotis, Stylianos, Wolzt, Michael
Format: Article
Language:English
Subjects:
Acetylcholine - pharmacology
Adult
Double-Blind Method
Endotoxemia - physiopathology
Endotoxins - toxicity
Escherichia coli
Forearm - blood supply
Humans
Inflammation
Male
N-Formylmethionine Leucyl-Phenylalanine - pharmacology
Neutrophils - drug effects
Neutrophils - physiology
Nitroglycerin - pharmacology
Norepinephrine - pharmacology
Oxidative Stress
Respiratory Burst
Simvastatin - pharmacology
Tumor Necrosis Factor-alpha - analysis
Vasodilation - drug effects
Vasodilation - physiology
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Summary: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. 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
ISSN:0009-7322
1524-4539
DOI:10.1161/01.cir.0000147774.90396.ed