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Role of Advanced Glycation Products with Oxidative Stress in Resistance Artery Dysfunction in Type 2 Diabetic mice
Author(s) -
Su Jun,
Lucchesi Pamela,
Suzuki Yasuhiro,
Rezk Bashir M,
Palen Desiree I,
Boulares Hamid A,
Matrougui khalid
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.964.13
Subject(s) - enos , medicine , endocrinology , endothelial dysfunction , oxidative stress , glycation , chemistry , nitric oxide , endothelium , myograph , nadph oxidase , diabetes mellitus , nitric oxide synthase
Diabetes is associated with increased advanced glycation end products (AGEs) formation and vasculopathy. We hypothesized that AGEs contribute to resistance artery dysfunction. Type 2 diabetic db−/db− (diabetic) and non‐diabetic db−/db+ (control) mice were treated with the AGEs inhibitor (aminoguanidine: 50 mg/Kg/day) for 3 months. Pressure‐induced myogenic tone (MT) was increased in mesenteric resistance arteries (MRAs) from diabetic mice but was unaffected by aminoguanidine treatment. Nitric oxide donor‐induced endothelium‐independent relaxation were similar in all groups. In diabetic mice, endothelium dependent relaxation in response to shear‐stress or acetylcholine was altered and was associated with reduced eNOS. Aminoguanidine treatment improved endothelial function and restored eNOS expression. Primary cultured endothelial cells (EC) subjected to high glucose for 48 hrs showed decreased eNOS expression and phosphorylation in response to calcium ionophore. High glucose decreased anti‐oxidant protein (MnSOD) and increased pro‐oxidant proteins (gp91phox) expression leading to increased oxidative stress generation, as assessed by DHE staining and endothelial NADH/NADPH oxidase activity. The pre‐incubation of endothelial cells with aminoguanidine restored eNOS‐phosphorylation and expression as well as the balance between pro‐ and anti‐oxidant factors induced by high glucose.