OBJECTIVETo investigate the effect of losartan on the expression of monocyte chemoattractant protein-1 (MCP1) and transforming growth factor-β(1) (TGF-β(1)) in the kidney of rats with unilateral urethral obstruction (UUO) and evaluate protective effect of losartan against reanal interstitial fibrosis.

METHODSRat models of UUO were treated with losartan at the routine dose, high dose, and very high dose (50, 200, and 500 mg/kg daily, respectively), and saline was given to UUO model rats and rats with sham operation. At 7, 14, and 21 days, the tail cuff blood pressure (TCP), 24-h urine protein (Upro), serum Scr, BUN, K(+), percentage of renal damage and renal interstitial fibrosis (%INT) were measured in the rats. MCP1 protein in the renal tissues was detected using immunohistochemistry, and MCP1 and TGF-β(1) mRNA expressions were assayed using RT-PCR.

RESULTSAs the UUO prolonged, Upro, TCP, tubular damage, %INT, and MCP1 and TGF-β(1) mRNA expressions all increased significantly (P<0.05). High and very high doses of losartan, compared with the routine dose, obviously reversed these changes.

CONCLUSIONHigh-dose losartan can effectively control blood pressure, reduce renal damage and fibrosis, and inhibit MCP1 and TGF-β(1) expression in rats with UUO, and at a very high dose, losartan can more effectively reduce 24-h Upro than the high-dose group. High and very high doses of losartan offer better protective effect on the kidney in rats with UUO.