Published Online
on August 26, 2002

A more recent version of this article appeared on September 17, 2002

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Submitted on May 24, 2002
Revised on July 6, 2002
Accepted on July 8, 2002

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, and 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.

^* To whom correspondence should be addressed. 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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