Document Detail


Recombinant human erythropoietin prevents lipopolysaccharide-induced vascular hyporeactivity in the rat.
MedLine Citation:
PMID:  18838949     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Erythropoietin (EPO) is a hypoxia-inducible hormone that is essential for normal erythropoiesis in the bone marrow. Administration of recombinant human-EPO is currently being used for the therapy of anemia associated with chronic renal failure and cancer. Moreover, EPO reduces organ injury in experimental hemorrhagic as well as in splanchnic artery occlusion shock and preserves cardiac function after experimental cardiac I/R. Erythropoietin receptors are widely distributed in the cardiovascular system, including endothelial, smooth muscle, cardiac, and other cell types, and nonhematopoietic effects of EPO are increasingly recognized. Thus, the vasculature may be a biological target of EPO. Therefore, the aim of our study was to investigate whether EPO exerts a protective effect in septic shock by modulating vascular dysfunction and hyporeactivity. Rats received EPO (300 U/kg, i.v.) or vehicle 30 min before and 1 and 3 h after LPS (8 x 10 U/kg, i.v.). In vivo and ex vivo (aortic rings) experiments were performed to evaluate the vascular response to contracting and vasodilating agents. The expression of iNOS, intercellular adhesion molecule 1, poly(ADP)ribose polymerase, Bcl-xl, and Bcl-2 was evaluated by Western blot analysis in the rat aorta. We demonstrate that EPO significantly prevents LPS-induced vascular hyporeactivity and endothelial dysfunction. Interestingly, EPO inhibits the increase in iNOS, poly(ADP)ribose polymerase, and intercellular adhesion molecule 1 expression in the aorta of endotoxemic rats and attenuated the decline in the expression of both Bcl-xl and Bcl-2 caused by LPS. In conclusion, our data support the view that EPO has important nonerythropoietic effects protecting organ and tissue against injury and indicate that EPO may be useful in the therapy of patients with septic shock.
Authors:
Roberta d'Emmanuele di Villa Bianca; Rosalinda Sorrentino; Emma Mitidieri; Stefania Marzocco; Giuseppina Autore; Christoph Thiemermann; Aldo Pinto; Raffaella Sorrentino
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Shock (Augusta, Ga.)     Volume:  31     ISSN:  1540-0514     ISO Abbreviation:  Shock     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-04-14     Completed Date:  2009-06-29     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9421564     Medline TA:  Shock     Country:  United States    
Other Details:
Languages:  eng     Pagination:  529-34     Citation Subset:  IM    
Affiliation:
Dipartimento di Farmacologia Sperimentale, Università degli studi di Napoli, Federico II, Italy.
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MeSH Terms
Descriptor/Qualifier:
Acetylcholine / pharmacology
Animals
Blotting, Western
Endothelium, Vascular / drug effects,  metabolism
Erythropoietin, Recombinant / pharmacology*
Humans
Intercellular Adhesion Molecule-1 / metabolism
Lipopolysaccharides / toxicity*
Male
Nitric Oxide Synthase Type II / metabolism
Poly(ADP-ribose) Polymerases / metabolism
Proto-Oncogene Proteins c-bcl-2 / metabolism
Rats
Rats, Wistar
Time Factors
Vascular Diseases / chemically induced,  metabolism,  prevention & control*
Vasoconstrictor Agents / pharmacology
Vasodilator Agents / pharmacology
bcl-X Protein / metabolism
Chemical
Reg. No./Substance:
0/Erythropoietin, Recombinant; 0/Lipopolysaccharides; 0/Proto-Oncogene Proteins c-bcl-2; 0/Vasoconstrictor Agents; 0/Vasodilator Agents; 0/bcl-X Protein; 126547-89-5/Intercellular Adhesion Molecule-1; 51-84-3/Acetylcholine; EC 1.14.13.39/Nitric Oxide Synthase Type II; EC 1.14.13.39/Nos2 protein, rat; EC 2.4.2.30/Poly(ADP-ribose) Polymerases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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