Effects of N-acetylcysteine against systemic and renal hemodynamic effects of endotoxin in healthy humans.
OBJECTIVE
Systemic inflammation causes vasodilation and impairs the vascular response to catecholamines. There is evidence that altered vasoreactivity is associated with increased production of free radicals. We studied the influence of systemic doses of the antioxidant N-acetylcysteine on inflammatory cytokines and renal plasma flow and on the systemic pressor response to norepinephrine during experimental endotoxemia.


METHODS
A double-blind, placebo-controlled crossover study.


METHODS
Medical University of Vienna, Clinical Pharmacology, Vienna General Hospital, AKH.


METHODS
Eight healthy, male humans.


METHODS
Intravenous administration of Escherichia coli endotoxin (lipopolysaccharide, 20 IU/kg) on two separate study days with concomitant intravenous infusion of placebo or N-acetylcysteine (150 mg/kg loading dose; 15 mg/kg/hr continuous infusion), respectively.


RESULTS
Measurements of inflammatory cytokines, of renal plasma flow by the para-aminohippurate-clearance method, and of the systemic pressor response to norepinephrine were taken at baseline and after endotoxin. Lipopolysaccharide increased body temperature and plasma concentrations of tumor necrosis factor-alpha, which was mitigated during N-acetylcysteine infusions. Likewise, the lipopolysaccharide-induced increases in renal plasma flow and decreases in blood pressure were attenuated, and the hyporeactivity of pulse rate to norepinephrine 4 hrs after lipopolysaccharide was improved by N-acetylcysteine.


CONCLUSIONS
High doses of N-acetylcysteine might exert protective effects on systemic hemodynamics and on the reactivity to catecholamines in humans challenged by lipopolysaccharide. This action of the antioxidant N-acetylcysteine is paralleled by humoral anti-inflammatory mechanisms and may be useful in patients with systemic inflammation.
Schaller
Georg
G
Department of Clinical Pharmacology, Medical University of Vienna, Austria.
Pleiner
Johannes
J
Mittermayer
Friedrich
F
Posch
Martin
M
Kapiotis
Stylianos
S
Wolzt
Michael
M
D000111:Acetylcysteine / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D001775:Blood Circulation / Q000187:drug effects; D018592:Cross-Over Studies; D016207:Cytokines / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007262:Infusions, Intravenous; D053583:Interleukin-1beta / Q000187:drug effects; D008070:Lipopolysaccharides; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects*; D018805:Sepsis / Q000188:drug therapy*; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects
D016207:Cytokines; D016166:Free Radical Scavengers; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D000111:Acetylcysteine