High doses of vitamin C reverse Escherichia coli endotoxin-induced hyporeactivity to acetylcholine in the human forearm

Article

关键词: ENDOTHELIUM-DEPENDENT DILATATION;    ASCORBIC-ACID;    NITRIC-OXIDE;    SUPEROXIDE-DISMUTASE;    OXIDATIVE STRESS;    INFLAMMATION;    PEROXYNITRITE;    DYSFUNCTION;    DISEASE;    INJURY;   

DOI  :  10.1161/01.CIR.0000030184.70207.FF

来源: SCIE

【 摘 要 】

Back-ground-Acute inflammation causes endothelial vasodilator dysfunction that may be mediated by oxidative stress. Methods and Results-In this randomized, double-blind, crossover study, forearm blood flow responses to acetylcholine (ACh) (endothelium-dependent dilator) and glyceryl-trinitrate (GTN) (endothelium-independent dilator) were assessed before and after induction of acute systemic inflammation by low doses of Escherichia coli endotoxin (LPS) (20 IU/kg IV) in 8 healthy volunteers. The acute effect of intra-arterial vitamin C (24 mg/min) or placebo was studied 4 hours after LPS, respectively. Vitamin C alone was administered in control experiments. LPS administration caused systemic vasodilation, increased white blood count, elevated body temperature, and reduced vitamin C plasma concentrations. LPS decreased the responses of forearm blood flow to ACh by 30% (P<0.05) but not to GTN. Vitamin C completely restored the response to ACh, which was comparable with that observed under baseline conditions. Vitamin C had no effect on basal blood flow or ACh- or GTN-induced vasodilation in control subjects. Conclusions-Our data demonstrate that impaired endothelial vasodilation caused by E coli endotoxemia can be counteracted by high doses of antioxidants in vivo. Oxidative stress may play an important role in the pathogenesis of endothelial dysfunction during inflammation.

【 授权许可】

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