Vascular methylglyoxal metabolism and the development of hypertension

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The pathogenic process of diabetes mellitus is associated with increased methylglyoxal (MG). MG causes non-enzymic glycation of proteins to form irreversible advanced glycation endproducts (AGEs). However, the correlation between MG and essential hypertension is unknown. The aim of the present study was to investigate whether MG, MG-induced AGEs, and oxidative stress were increased in the aorta of spontaneously hypertensive rats (SHR) and whether an increased formation of MG and related AGEs was correlated with the development of high blood pressure in these rats. High-performance liquid chromatography (HPLC) was used to determine MG and reduced glutathione levels in plasma and aorta. MG-induced AGEs, N(epsilon)-carboxyethyl-lysine (CEL) and N(epsilon)-carboxymethyl-lysine (CML), in aorta were determined using immunohistochemistry. Hydrogen peroxide and superoxide levels in aorta and glutathione peroxidase and reductase activities were also determined. Aortic and plasma MG levels were significantly elevated in SHR, but not in Wistar-Kyoto (WKY) rats, at 8, 13 and 20 weeks of age, in parallel with blood pressure increase. Immunohistochemistry revealed more intense staining for CML and CEL in aorta from SHR than those of WKY rats from 8 weeks onwards. Most of the staining was localized to endothelial cells. Superoxide and hydrogen peroxide levels were significantly elevated in aorta of SHR at 13 weeks, whereas reduced glutathione levels, glutathione peroxidase and glutathione reductase activities were significantly decreased compared to WKY rats. Increased aortic MG, AGE formation and oxidative stress were associated with blood pressure increase in SHR, which may cause endothelial dysfunction and altered vascular reactivity.