Increased methylglyoxal and advanced glycation end products in kidney from spontaneously hypertensive rats.
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, Nepsilon-carboxyethyl-lysine (CEL), and Nepsilon-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.


CONCLUSIONS
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.
Wang
Xiaoxia
X
Department of Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Desai
Kaushik
K
Clausen
Jes Thorn
JT
Wu
Lingyun
L
D000367:Age Factors; D000818:Animals; D019803:Glutathione Disulfide / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006977:Hypertension, Renal / Q000378:metabolism*; D007668:Kidney / Q000201:enzymology*; D008297:Male; D018384:Oxidative Stress / Q000502:physiology; D011765:Pyruvaldehyde / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D017127:Glycation End Products, Advanced; D011765:Pyruvaldehyde; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D019803:Glutathione Disulfide