Human serum albumin improves arterial dysfunction during early resuscitation in mouse endotoxic model via reduced oxidative and nitrosative stresses.
Human serum albumin (HSA) is used as a resuscitation fluid in sepsis. This study investigated the potential protective properties of HSA on vascular function in a mouse endotoxic model in terms of oxidative and nitrosative stresses. Swiss mice were treated with either lipopolysaccharide (LPS) (50 mg/kg i.p.) or vehicle. One and five hours later, mice were infused with HSA (4%, 10 ml/kg), normal saline (0.9% NaCl, 30 ml/kg), or no fluid. Six hours after treatment, vascular reactivity was assessed on aortae and small mesenteric arteries. Measurements of NO and superoxide anion (O2(-)) by spin trapping and nuclear factor (NF)-kappaB, inducible NO synthase (iNOS), and peroxynitrite by Western blotting and immunohistochemical studies were conducted. HSA partially prevented the reduction of blood pressure induced by LPS and completely prevented both vascular hyporeactivity to phenylephrine and myogenic tone as well as endothelial dysfunction induced by the endotoxin. This was associated with a decreased up-regulation of NF-kappa B, iNOS, and peroxynitrite in the vascular wall. LPS-induced tissue increases in both NO and O2(-) production was decreased by HSA. These data demonstrate the protective effect of HSA treatment in experimental endotoxic shock by reducing the inflammatory process leading to oxidative and nitrosative stresses and vascular hyporeactivity.
Meziani
Ferhat
F
INSERM UMR 771 Angers, CNRS UMR 6214, Faculté de Médecine, rue Haute de Reculée, 49000 Angers, France.
Kremer
Hélène
H
Tesse
Angela
A
Baron-Menguy
Céline
C
Mathien
Cyrille
C
Mostefai
H Ahmed
HA
Carusio
Nunzia
N
Schneider
Francis
F
Asfar
Pierre
P
Andriantsitohaina
Ramaroson
R
D000818:Animals; D001011:Aorta / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D004195:Disease Models, Animal; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity; D008638:Mesenteric Arteries / Q000187:drug effects; D051379:Mice; D016328:NF-kappa B / Q000032:analysis; D009569:Nitric Oxide / Q000032:analysis; D052247:Nitric Oxide Synthase Type II / Q000032:analysis; D018384:Oxidative Stress / Q000187:drug effects; D012151:Resuscitation; D012709:Serum Albumin / Q000494:pharmacology / Q000627:therapeutic use*; D012772:Shock, Septic / Q000188:drug therapy*; D013481:Superoxides / Q000032:analysis; D014664:Vasodilation / Q000187:drug effects*
D008070:Lipopolysaccharides; D016328:NF-kappa B; D012709:Serum Albumin; D013481:Superoxides; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II