Renoprotective effects of azelnidipine, a dihydropyridine-based calcium antagonist in advanced glycation end product (AGE)-injected rats.
Diabetic nephropathy is a leading cause of end-stage renal disease in industrialized countries. Although the molecular mechanisms for the development and progression of diabetic nephropathy are not fully understood, the formation and accumulation of advanced glycation end products (AGEs) have been considered to play a major role in the pathogenesis of diabetic nephropathy. Hypertension is also an independent risk factor for the progression of diabetic nephropathy. However, functional cross-talk between AGEs and blood pressure and their involvement in diabetic nephropathy remain to be elucidated. In this study, we examined the effects of oral administration of azelnidipine, a commercially available dihydropyridine-based calcium antagonist, on renal injury in AGE-treated rats. Administration of azelnidipine inhibited the increase of systolic and diastolic blood pressure levels and urinary N-acetyl-beta-D-glucosaminidase activity in exogenously AGE-injected rats. Furthermore, azelnidipine treatment also prevented glomerulosclerosis in AGE-treated rats. These results indicate that renal damage in AGE-injected rats could be mediated, at least in part, by the elevation of blood pressure. Our present study suggests that azelnidipine would represent a valuable drug for the treatment of diabetic nephropathy by blocking the deleterious effects of AGEs.
Yamagishi
S
S
Department of Medicine, Kurume University School of Medicine, Japan. shoichi@med.kurume-u.ac.jp
Takeuchi
M
M
Inoue
H
H
D000117:Acetylglucosamine / Q000652:urine; D000818:Animals; D001383:Azetidinecarboxylic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000037:antagonists & inhibitors*; D004095:Dihydropyridines / Q000494:pharmacology*; D017127:Glycation End Products, Advanced / Q000633:toxicity*; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000378:metabolism; D013997:Time Factors
D004095:Dihydropyridines; D017127:Glycation End Products, Advanced; D012709:Serum Albumin; D001383:Azetidinecarboxylic Acid; C061679:azelnidipine; D002118:Calcium; D000117:Acetylglucosamine