Hyperglycaemia-induced impairment of endothelium-dependent vasorelaxation in rat mesenteric arteries is mediated by intracellular methylglyoxal levels in a pathway dependent on oxidative stress

• DOI: 10.1007/s00125-010-1677-0
• Publication Date: 2010-02-25T05:59:08Z
• Authors: O. Brouwers; P. M. Niessen; G. Haenen; T. Miyata; M. Brownlee; C. D. Stehouwer; J. G. De Mey; C. G. Schalkwijk
• Keywords: Mesenteric arteries

Impaired nitric oxide (NO)-dependent vasorelaxation plays a key role in the development of diabetic vascular complications. We investigated effect hyperglycaemia on impaired vasoreactivity and putative therein AGE precursor methylglyoxal. The effects high glucose methylglyoxal NO-dependent isolated rat mesenteric arteries from wild-type transgenic glyoxalase (GLO)-I (also known as GLO1) rats, i.e. enzyme detoxifying methylglyoxal, were recorded wire myograph. formation major methylglyoxal-adduct 5-hydro-5-methylimidazolone (MG-H1) was detected with an antibody against MG-H1 quantified ultra-performance liquid chromatography (tandem) mass spectrometry. Reactive oxygen species measured 5-(and-6)-chloromethyl-2′7′-dichlorodihydrofluorescein diacetate acetyl ester probe by immunohistochemistry nitrotyrosine. High exposure significantly reduced efficacy (p < 0.05). This impairment not observed GLO-I rats indicating specific intracellular effect. diabetes-induced potency (pD2) improved overexpression Methylglyoxal-modified albumin did affect vasorelaxation, while under same conditions receptor for ligand S100b Methylglyoxal treatment increased staining endothelial cells adventitia fivefold accompanied eightfold increase oxidative stress marker Antioxidant pre-incubation prevented methylglyoxal-induced vasoreactivity. These data show that hyperglycaemia-induced endothelium-dependent is mediated levels pathway dependent stress.