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Endothelial dysfunction in rat adjuvant-induced arthritis: Upregulation of the vascular arginase pathway.
MedLine Citation:
PMID:  21484767     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
OBJECTIVE: To investigate whether arginase pathway abnormalities occurs in vessels from adjuvant-induced arthritis (AIA) rats, and whether the upregulation of arginase, which reciprocally regulates nitric oxide (NO) synthase by competing for the same substrate, L-arginine, contributes to endothelial dysfunction in AIA. METHODS: Vascular reactivity experiments were performed on thoracic aortic rings from AIA rats and control rats, and investigated the response of rings to norepinephrine (NE), sodium nitroprussiate (SNP) and acetylcholine (Ach). Ach-induced relaxation was evaluated in presence or not of the NOS inhibitor N(W) -nitro-L-arginine methyl ester (L-NAME), the arginase inhibitor Nω-hydroxy-nor-arginine (nor-NOHA) or both. Aortic arginase activity was measured by spectrophotometric method and expression of arginase as well as endothelial NO synthase (eNOS) were evaluated by Western blotting. RESULTS: Ach-induced vasodilation was significantly impaired in AIA rats, whereas the response to NE and to SNP were not different from control rats. L-NAME reduced Ach-induced vasodilation to a lesser extent in AIA rats compared to control rats. Incubation of aortic rings with nor-NOHA enhanced the vascular response to Ach in AIA rats and reversed the effects of L-NAME. AIA rats exhibited increased vascular expression of arginase II (+22%, p<0.05) as well as increased arginase activity (+49%, p<0.05) whereas eNOS expression was unchanged. Finally, arginase activity and expression positively correlates with arthritis severity. CONCLUSIONS: Our results argue for a role of arginase upregulation in AIA-associated endothelial dysfunction. They suggest that arginase might be a new attractive target for treating endothelial dysfonction in arthritis.
Authors:
Clément Prati; Alain Berthelot; Daniel Wendling; Céline Demougeot
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-4-11
Journal Detail:
Title:  Arthritis and rheumatism     Volume:  -     ISSN:  1529-0131     ISO Abbreviation:  -     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-4-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370605     Medline TA:  Arthritis Rheum     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 by the American College of Rheumatology.
Affiliation:
Pôle « Dysfonction Endothéliale », EA 4267 « Sciences Séparatives Biologiques et Pharmaceutiques », Faculté de Médecine-Pharmacie, 25030 BESANCON, France; University Hospital of Besançon, Rheumatology and University Of Franche Comté, EA4266. F-25000 BESANCON, France.
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