Format

Send to

Choose Destination
J Am Coll Cardiol. 2003 Nov 5;42(9):1656-62.

Inflammation-induced vasoconstrictor hyporeactivity is caused by oxidative stress.

Author information

1
Department of Clinical Pharmacology, University of Vienna, Vienna, Austria.

Abstract

OBJECTIVES:

We sought to determine the role of oxidative stress in the development of vascular dysfunction in inflammation.

BACKGROUND:

Hyporeactivity to catecholamines and other vasoconstrictors is present in acute inflammation. Because oxidative stress plays a significant role in inflammation, impaired responsiveness may be overcome by anti-oxidants.

METHODS:

In randomized, double-blind, cross-over studies, forearm blood flow (FBF) responses to norepinephrine (NE), angiotensin II (ANG II), and vasopressin (VP) were assessed before and 4 h after induction of systemic inflammation by low doses of Escherichia coli endotoxin (lipopolysaccharide [LPS], 20 IU/kg intravenously) or after placebo in healthy volunteers. Furthermore, the effect of intra-arterial vitamin C (24 mg/min) or placebo on NE-induced or ANG II-induced vasoconstriction was studied after LPS.

RESULTS:

Administration of LPS caused systemic and forearm vasodilation, increased white blood cell count, elevated body temperature, and reduced vitamin C plasma concentrations. Lipopolysaccharide decreased the responses of FBF to NE by 59%, to ANG II by 25%, and to VP by 51% (n = 9, p < 0.05, all effects). Co-administration of vitamin C completely restored the response to NE and to ANG II, which was comparable to that observed under baseline conditions (n = 8).

CONCLUSIONS:

E. coli-endotoxemia reduces FBF responsiveness to vasoconstrictors. The hyporeactivity can be corrected by high doses of vitamin C, suggesting that oxidative stress may represent an important target for inflammation-induced impaired vascular function.

PMID:
14607455
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center