Inflammation-induced vasoconstrictor hyporeactivity is caused by oxidative stress.
OBJECTIVE
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.
Pleiner
Johannes
J
Department of Clinical Pharmacology, University of Vienna, Vienna, Austria.
Mittermayer
Friedrich
F
Schaller
Georg
G
Marsik
Claudia
C
MacAllister
Raymond J
RJ
Wolzt
Michael
M
D000328:Adult; D000804:Angiotensin II / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D019446:Endotoxemia / Q000503:physiopathology*; D004927:Escherichia coli Infections / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D008297:Male; D018384:Oxidative Stress; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014667:Vasopressins / Q000494:pharmacology*
D000975:Antioxidants; D014662:Vasoconstrictor Agents; D014667:Vasopressins; D000804:Angiotensin II; D001205:Ascorbic Acid