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.