High doses of vitamin C reverse Escherichia coli endotoxin-induced hyporeactivity to acetylcholine in the human forearm.
BACKGROUND
Acute inflammation causes endothelial vasodilator dysfunction that may be mediated by oxidative stress.


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.
Pleiner
Johannes
J
Department of Clinical Pharmacology, University of Vienna, Austria.
Mittermayer
Friedrich
F
Schaller
Georg
G
MacAllister
Raymond J
RJ
Wolzt
Michael
M
D000109:Acetylcholine / Q000494:pharmacology*; D000328:Adult; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D004926:Escherichia coli; D005542:Forearm / Q000098:blood supply; D006801:Humans; D007249:Inflammation / Q000382:microbiology / Q000503:physiopathology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology; D018384:Oxidative Stress; D010991:Plethysmography; D012039:Regional Blood Flow / Q000187:drug effects; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology*
D000975:Antioxidants; D008070:Lipopolysaccharides; D014665:Vasodilator Agents; D005996:Nitroglycerin; D000109:Acetylcholine; D001205:Ascorbic Acid