Olmesartan medoxomil, a newly developed angiotensin II type 1 receptor antagonist, protects against renal damage 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 of advanced glycation end products (AGEs) and activation of the renin-angiotensin system (RAS) have been considered to be the main factors participating in the pathogenesis of diabetic nephropathy. However, functional cross-talk between AGEs and the RAS remains to be elucidated. In this study, we examined the effects of oral administration of olmesartan medoxomil, a newly developed angiotensin II type 1 receptor antagonist, on renal damage in AGE-treated rats. Administration of olmesartan medoxomil significantly inhibited the increase of systolic and diastolic blood pressure levels and urinary N-acetyl-beta-D-glucosaminidase activity in exogenously AGE-injected rats. Furthermore, olmesartan medoxomil treatment also prevented glomerulosclerosis in AGE-treated rats. These results indicate that exogenous AGE treatment could induce renal damage via the activation of the RAS. Our study suggests that olmesartan medoxomil could be 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, Kurume, Japan. shoichi@med.kurume-u.ac.jp
Takeuchi
M
M
Inoue
H
H
D000117:Acetylglucosamine / Q000652:urine; D057912:Angiotensin II Type 2 Receptor Blockers; D000818:Animals; D001835:Body Weight; D005923:Glomerulosclerosis, Focal Segmental / Q000473:pathology / Q000517:prevention & control; D017127:Glycation End Products, Advanced / Q000633:toxicity*; D007093:Imidazoles / Q000627:therapeutic use*; D007674:Kidney Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D008297:Male; D000068557:Olmesartan Medoxomil; D011507:Proteinuria / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D020239:Receptor Cross-Talk; D012084:Renin-Angiotensin System / Q000187:drug effects; D013777:Tetrazoles / Q000627:therapeutic use*; D016707:Tissue Fixation
D057912:Angiotensin II Type 2 Receptor Blockers; D017127:Glycation End Products, Advanced; D007093:Imidazoles; D013777:Tetrazoles; D000068557:Olmesartan Medoxomil; D000117:Acetylglucosamine