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 andplasma tumor necrosis factor-alpha 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.
RCT Entities:
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-alpha 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.
Authors: J Jin; X Zhang; Z Lu; Y Li; M F Lopes-Virella; H Yu; C J Haycraft; Q Li; K L Kirkwood; Y Huang Journal: J Periodontal Res Date: 2013-10-07 Impact factor: 4.419
Authors: Sharon M L Wallace; Kaisa M Mäki-Petäjä; Joseph Cheriyan; Edward H Davidson; Lynne Cherry; Carmel M McEniery; Naveed Sattar; Ian B Wilkinson; Rajesh K Kharbanda Journal: Br J Clin Pharmacol Date: 2010-12 Impact factor: 4.335
Authors: Alessandro Morandi; Christopher G Hughes; Jennifer L Thompson; Pratik P Pandharipande; Ayumi K Shintani; Eduard E Vasilevskis; Jin H Han; James C Jackson; Daniel T Laskowitz; Gordon R Bernard; E Wesley Ely; Timothy D Girard Journal: Crit Care Med Date: 2014-08 Impact factor: 7.598