title: An angiotensin II type-I receptor blocker, olmesartan medoxomil, attenuates lipid peroxidation in renal injury induced by subtotal nephrectomy.
abstract: BACKGROUND
  Lipid-related oxidative stress, such as that caused by malondialdehyde (MDA), acrolein, and 4-hydroxynonenal (4-HNE), is involved in vascular injury in diabetes and hypertension. Olmesartan medoxomil, a blocker of angiotensin II type-I receptor, is an antihypertensive drug with antioxidant properties. In this study, we examined the involvement of oxidative lipids and the effect of olmesartan on lipid peroxidation in the progressive renal injury induced by renal mass reduction in rats.
  
  
  METHODS
  Rats were treated with vehicle or olmesartan (0.5 mg/kg or 10 mg/kg) for up to 8 weeks after subtotal nephrectomy. The expression of oxidative lipids and the effect of olmesartan on lipid peroxidation were evaluated by Western blotting and immunostaining of renal tissue.
  
  
  RESULTS
  Immunohistochemical examination revealed that MDA, acrolein, and 4-HNE were scarcely detected in renal cortex in sham-operated rats. On the contrary, these oxidative lipids were observed in injured glomeruli and dilated renal tubules in the ablated kidneys. Western blotting of renal cortical tissue revealed that MDA- or acrolein-bound proteins were mainly detected in the range of 30-90 kDa. Treatment with olmesartan attenuated lipid peroxidation and glomerulosclerosis. The renoprotective and antioxidative effect was higher in rats that received a high dose of olmesartan than in rats in the low-dose group.
  
  
  CONCLUSIONS
  These results indicate that oxidative lipids reflect the progression of renal injury induced by subtotal nephrectomy in rats. Olmesartan may have a renoprotective effect, with attenuation of lipid peroxidation.
authors: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan.
authors: Toshiyuki
authors: T
authors: Takahashi
authors: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan. kkonta@med.id.yamagata-u.ac.jp.
authors: Tsuneo
authors: T
authors: Konta
authors: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan.
authors: Satoshi
authors: S
authors: Takasaki
authors: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan.
authors: Kazunobu
authors: K
authors: Ichikawa
authors: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan.
authors: Yasuchika
authors: Y
authors: Takeishi
authors: Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan.
authors: Isao
authors: I
authors: Kubota
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001794:Blood Pressure; D001835:Body Weight; D007093:Imidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects / Q000293:injuries* / Q000473:pathology; D007678:Kidney Glomerulus / Q000293:injuries / Q000473:pathology; D050356:Lipid Metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D009392:Nephrectomy; D000068557:Olmesartan Medoxomil; D009929:Organ Size; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D051437:Renal Insufficiency / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D013777:Tetrazoles / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D007093:Imidazoles; D011506:Proteins; D013777:Tetrazoles; D000068557:Olmesartan Medoxomil