Effect of losartan pretreatment on kidney lipid content after unilateral obstruction in rats

Intrarenal concentration of angiotensin II increases after the onset of ureteral obstruction in the obstructed kidney. The effect of pretreatment with losartan, a specific angiotensin II AT1 receptor antagonist, on lipid contents, which were previously modified by unilateral ureteral obstruction (UUO), was studied in renal cortex of rats. Adult Wistar Kyoto rats were subjected to either UUO for 24 hr or control sham operation after being treated with losartan in the drinking water at 10 mg/kg rat/day for 15 days. In the cortex of obstructed kidney the increased free and esterified cholesterol concentrations were associated with the increased cholesterol synthesis measured by incorporation of 14C-acetate (0.001>p), compared with control and contralateral kidneys. The increased amount of phosphatidylcholine was related with the increased incorporation of 14C-choline into phosphatidylcholine (0.01>p). Phosphatidylethanolamine and sphingomyelin decreased slightly but total phospholipid content did not change. The level of AT1 receptor mRNA in obstructed kidney was significantly lower than in control and contralateral kidneys. Losartan pretreatment attenuated (0.01>p) the increase in cholesterol content and synthesis and restored and enhanced the AT1 angiotensin II receptor gene expression. The interference in the renin-angiotensin system before UUO may modify renal cortex cholesterol content.