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.
RCT Entities:
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.
Authors: A Mancini; R Festa; V Di Donna; E Leone; G P Littarru; A Silvestrini; E Meucci; A Pontecorvi Journal: J Endocrinol Invest Date: 2010-06 Impact factor: 4.256
Authors: Abraham C I van Steen; Lanette Kempers; Rouven Schoppmeyer; Max Blokker; David J Beebe; Martijn A Nolte; Jaap D van Buul Journal: J Cell Sci Date: 2021-11-04 Impact factor: 5.285
Authors: Mark van den Boogaard; Bart P Ramakers; Nens van Alfen; Sieberen P van der Werf; Wilhelmina F Fick; Cornelia W Hoedemaekers; Marcel M Verbeek; Lisette Schoonhoven; Johannes G van der Hoeven; Peter Pickkers Journal: Crit Care Date: 2010-05-05 Impact factor: 9.097