An angiotensin II type-I receptor blocker, olmesartan medoxomil, attenuates lipid peroxidation in renal injury induced by subtotal nephrectomy.
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.
Takahashi
Toshiyuki
T
Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan.
Konta
Tsuneo
T
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.
Takasaki
Satoshi
S
Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan.
Ichikawa
Kazunobu
K
Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan.
Takeishi
Yasuchika
Y
Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan.
Kubota
Isao
I
Department of Cardiology, Pulmonology, and Nephrology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan.
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
D047228:Angiotensin II Type 1 Receptor Blockers; D007093:Imidazoles; D011506:Proteins; D013777:Tetrazoles; D000068557:Olmesartan Medoxomil