Suppression of vascular inflammation by kinin b1 receptor antagonism in a rat model of insulin resistance

Jenny Pena Dias, Réjean Couture

Research output: Contribution to journalArticle

Abstract

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 (homeostasis model assessment index), and on protein or mRNA expression of the following target genes in the aorta (by Western blot and real-time quantitative polymerase chain reaction): B1R, endothelial nitric oxide synthase, inducible nitric oxide synthase, macrophage CD68, macrophage/monocyte CD11b, interleukin (IL)-1β, tumor necrosis factor-α, IL-6, macrophage migration inhibitory factor, intercellular 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 endothelial nitric oxide synthase and tumor necrosis factor-α, which were not affected. SSR240612 reversed hyperglycemia, hyperinsulinemia, insulin resistance, and the upregulation of B1R, inducible nitric oxide synthase, macrophage CD68, and CD11b, IL-1β, inter-cellular adhesion molecule-1, macrophage migration inhibitory factor, and E-selectin in glucose-fed rats, yet it had no significant effect on IL-6 and in control rats. Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)61-69
Number of pages9
JournalJournal of Cardiovascular Pharmacology
Volume60
Issue number1
DOIs
StatePublished - Jul 1 2012
Externally publishedYes

Fingerprint

Kinins
Blood Vessels
Insulin Resistance
Inflammation
Glucose
Macrophage Migration-Inhibitory Factors
Aorta
E-Selectin
Macrophages
Nitric Oxide Synthase Type II
Interleukin-1
Interleukin-6
Up-Regulation
Tumor Necrosis Factor-alpha
Nitric Oxide Synthase Type III
Hyperinsulinism
Intercellular Adhesion Molecule-1
Hyperglycemia
Type 2 Diabetes Mellitus
Sprague Dawley Rats

Keywords

  • adhesion molecules
  • bradykinin
  • cytokines
  • insulin resistance
  • kinin B receptor
  • macrophage
  • vascular inflammation

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

Suppression of vascular inflammation by kinin b1 receptor antagonism in a rat model of insulin resistance. / Pena Dias, Jenny; Couture, Réjean.

In: Journal of Cardiovascular Pharmacology, Vol. 60, No. 1, 01.07.2012, p. 61-69.

Research output: Contribution to journalArticle

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