Published online before print November 8, 2007

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Copyright © 2007 American Society for Investigative Pathology
American Journal of Pathology, doi:10.2353/ajpath.2007.070316

Accepted for publication September 5, 2007.

Article

Human Serum Albumin Improves Arterial Dysfunction during Early Resuscitation in Mouse Endotoxic Model via Reduced Oxidative and Nitrosative Stresses

Ferhat Meziani^*, Hélène Kremer, Angela Tesse^*, Céline Baron-Menguy^*, Cyrille Mathien, H. Ahmed Mostefai^*, Nunzia Carusio^*, Francis Schneider, Pierre Asfar, and Ramaroson Andriantsitohaina^*@

From INSERM UMR 771,* Angers; CNRS UMR 6214, Angers; Université d'Angers, UFR de Médecine, Angers; the Institut Gilbert-Laustriat, CNRS UMR 7175-LC1, Illkirch; Université de Strasbourg, Faculté de Pharmacie, Strasbourg, France; the Département de Réanimation Médicale et de Médecine Hyperbare, CHU, Angers; and the Service de Réanimation Médicale, Hôpitaux Universitaires de Strasbourg, Strasbourg, France

^@ To whom correspondence should be addressed. E-mail: ramaroson.andriantsitohaina{at}univ-angers.fr.

	Abstract

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)-B, 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- 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.