Increased methylglyoxal and advanced glycation end products in kidney from spontaneously hypertensive rats

Abstract

Background. Methylglyoxal (MG), a metabolite of glucose, causes nonenzymatic glycation of proteins to form irreversible advanced glycation end products (AGEs). The role of MG in the development of essential hypertension is unknown, although MG has been extensively studied in relation to diabetes. Methods. Blood pressure of spontaneously hypertensive rats (SHR) and paired Wistar Kyoto (WKY) rats was measured at 5, 8, 13, and 20 weeks of age. HPLC was used to determine the levels of plasma and kidney MG, as well as reduced or oxidized glutathione in the kidney. MG-induced AGEs, Nε- carboxyethyl-lysine (CEL), and Nε-carboxymethyl-lysine (CML) in the kidney were detected by immunohistochemistry. Glutathione peroxidase and reductase activities in the kidney were also determined. Results. Plasma MG levels were significantly elevated in SHR, but not in WKY rats, at 8, 13, and 20 weeks of age in parallel with blood pressure increase. Kidney MG levels in SHR were increased by 21% and 38% at 13 and 20 weeks, respectively, compared to age-matched WKY rats. There were no differences in blood pressure and MG levels in plasma and kidney between SHR and WKY rats at 5 weeks of age. Immunohistochemistry revealed more intense staining for CML and CEL in kidneys from SHR compared to WKY rats from 8 weeks onward. Most of the staining was localized to renal tubules with some staining in the glomerular vessels. Conclusion. MG and AGEs formation was significantly elevated in kidney from SHR, which may cause local vascular and tubular damage, contributing to the development and complications of hypertension. © 2004 by the International Society of Nephrology.