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(Circulation. 2002;106:1460.)
© 2002 American Heart Association, Inc.

Clinical Investigation and Reports

High Doses of Vitamin C Reverse Escherichia coli Endotoxin–Induced Hyporeactivity to Acetylcholine in the Human Forearm

Johannes Pleiner, MD; Friedrich Mittermayer, MD; Georg Schaller, MD; Raymond J. MacAllister, MD, FRCP; Michael Wolzt, MD

From the Department of Clinical Pharmacology, University of Vienna, Austria, and Centre for Clinical Pharmacology and Therapeutics (R.J.M.), Department of Medicine, University College London, UK.

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

Background— 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.

Key Words: inflammation • endothelial function • oxidative stress • vitamin C

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