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Suppression of vascular inflammation by kinin B1 receptor antagonism in a rat model of insulin resistance.
MedLine Citation:
PMID:  22494994     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND: Kinin B1 receptor (B1R) intervenes in a positive feedback loop to amplify and perpetuate the vascular oxidative stress in glucose-fed rats, a model of insulin resistance. This study aims at determining whether B1R blockade could reverse vascular inflammation in this model. METHODS/RESULTS: Young male Sprague-Dawley rats were fed with 10% D-glucose or tap water (controls) for 8 weeks and during the last week, rats were administered the B1R antagonist SSR240612 (10 mg/kg/day, gavage) or the vehicle. The outcome was determined on glycemia, insulinemia, insulin resistance (HOMA index) and on protein or mRNA expression of the following target genes in the aorta (by Western blot and qRT-PCR): B1R, eNOS (endothelial nitric oxidase synthase), iNOS (inducible nitric oxidase synthase), macrophage CD68, macrophage/monocyte CD11b, IL-1β (interleukin-1β), TNF-α (tumor necrosis factor-α), IL-6 (interleukin-6), MIF (macrophage migration inhibitory factor), ICAM-1 (inter-cellular adhesion molecule-1) and E-selectin (endothelial adhesion molecule). Data showed increased expression of all these markers in the aorta of glucose-fed rats except eNOS and TNF-α which were not affected. SSR240612 reversed hyperglycemia, hyperinsulinemia, insulin resistance and the upregulation of B1R, iNOS, macrophage CD68 and CD11b, IL-1β, ICAM-1, MIF and E-selectin in glucose-fed rats, yet it had no significant effect on IL-6 and in control rats. CONCLUSION: Kinin B1R antagonism reversed the upregulation of its own receptor and several pro-inflammatory markers in the aorta of glucose-fed rats. These data provide the first evidence that B1R may contribute to the low-grade vascular inflammation in insulin resistance, an early event in the development of type 2 diabetes.
Authors:
Jenny Pena Dias; Réjean Couture
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-4-10
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  -     ISSN:  1533-4023     ISO Abbreviation:  -     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-4-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Physiology, Faculty of Medicine, Université de Montréal, Montréal, QC, Canada H3C 3J7.
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