Kinin B1 receptor enhances the oxidative stress in a rat model of insulin resistance: outcome in hypertension, allodynia and metabolic complications

Kinin B(1) receptor (B(1)R) is induced by the oxidative stress in models of diabetes mellitus. This study aims at determining whether B(1)R activation could perpetuate the oxidative stress which leads to diabetic complications. Young Sprague-Dawley rats were fed with 10% D-Glucose or tap water (cont...

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Bibliographic Details
Published in:PloS one 2010-09, Vol.5 (9), p.e12622
Main Authors: Dias, Jenny Pena, Talbot, Sébastien, Sénécal, Jacques, Carayon, Pierre, Couture, Réjean
Format: Article
Language:English
Subjects:
Abdomen
Abnormalities
Activation
Allopurinol
Animal models
Animals
Aorta
Binding sites
Blood
Blood pressure
Blood Pressure - drug effects
Bradykinin B1 Receptor Antagonists
Cardiovascular Disorders/Hypertension
Catalase
Complications
Coronary vessels
Diabetes
Diabetes and Endocrinology/Type 2 Diabetes
Diabetes Complications - drug therapy
Diabetes Complications - metabolism
Diabetes Complications - physiopathology
Diabetes mellitus
Dioxoles - administration & dosage
Disease Models, Animal
Drinking water
Drug dosages
Enzymes
Gastrocnemius muscle
Gene expression
Glucose
Humans
Hyperalgesia - drug therapy
Hyperalgesia - metabolism
Hyperalgesia - physiopathology
Hypertension
Hypertension - drug therapy
Hypertension - metabolism
Hypertension - physiopathology
Insulin
Insulin Resistance
Ischemia
Kinins
Liver
Low temperature resistance
Male
Medical research
Medicine
NAD(P)H oxidase
NADPH Oxidases - genetics
NADPH Oxidases - metabolism
Neuroscience/Sensory Systems
NG-Nitroarginine methyl ester
Nitric oxide
Nitric-oxide synthase
Oxidation resistance
Oxidative Stress
Pain
Pain perception
Pharmacology
Physiology
Physiology/Integrative Physiology
Plasma levels
Rats
Rats, Sprague-Dawley
Receptor, Bradykinin B1 - genetics
Receptor, Bradykinin B1 - metabolism
Rodents
Spinal cord
Studies
Sulfonamides - administration & dosage
Superoxide dismutase
Superoxide Dismutase - genetics
Superoxide Dismutase - metabolism
Tactile
Tactile stimuli
Thrombosis
Xanthine oxidase
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Summary:Kinin B(1) receptor (B(1)R) is induced by the oxidative stress in models of diabetes mellitus. This study aims at determining whether B(1)R activation could perpetuate the oxidative stress which leads to diabetic complications. Young Sprague-Dawley rats were fed with 10% D-Glucose or tap water (controls) for 8-12 weeks. A selective B(1)R antagonist (SSR240612) was administered acutely (3-30 mg/kg) or daily for a period of 7 days (10 mg/kg) and the impact was measured on systolic blood pressure, allodynia, protein and/or mRNA B(1)R expression, aortic superoxide anion (O(2)(*-)) production and expression of superoxide dismutase (MnSOD) and catalase. SSR240612 reduced dose-dependently (3-30 mg/kg) high blood pressure in 12-week glucose-fed rats, but had no effect in controls. Eight-week glucose-fed rats exhibited insulin resistance (HOMA index), hypertension, tactile and cold allodynia and significant increases of plasma levels of glucose and insulin. This was associated with higher aortic levels of O(2)(*-), NADPH oxidase activity, MnSOD and catalase expression. All these abnormalities including B(1)R overexpression (spinal cord, aorta, liver and gastrocnemius muscle) were normalized by the prolonged treatment with SSR240612. The production of O(2)(*-) in the aorta of glucose-fed rats was also measured in the presence and absence of inhibitors (10-100 microM) of NADPH oxidase (apocynin), xanthine oxidase (allopurinol) or nitric oxide synthase (L-NAME) with and without Sar[D-Phe(8)]des-Arg(9)-BK (20 microM; B(1)R agonist). Data show that the greater aortic O(2)(*-) production induced by the B(1)R agonist was blocked only by apocynin. Activation of kinin B(1)R increased O(2)(*-) through the activation of NADPH oxidase in the vasculature. Prolonged blockade of B(1)R restored cardiovascular, sensory and metabolic abnormalities by reducing oxidative stress and B(1)R gene expression in this model.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0012622