Lead intoxication is usually insidious and may cause a variety of complications such as kidney damage and hypertension. The role of intrarenal renin-angiotensin system (RAS) in lead-induced nephropathy has not been investigated. Adult male Sprague-Dawley rats were fed with water containing 250 ppm of lead acetate (lead group) and deionized water (control group) for 4 weeks. Another two groups started to receive intraperitoneal captopril (50 mg/kg/d) or losartan (10 mg/kg/d) after 2 weeks of lead feeding and continued for another 2 weeks. Immunoblotting was used to analyze the protein amount of intrarenal RAS components and transforming growth factor-beta (TGF-beta). Compared with control group, lead exposure resulted in increased proteinuria after 2-week treatment (4.2 +/- 0.9 mg/100 g vs. 1.8 +/- 0.8 mg/100 g, p < 0.05) and 4-week (5.2 +/- 1.7 mg/100 g, p < 0.05). Serum creatinine level was increased (0.40 +/- 0.2 vs. 0.3 +/- .04 mg/dL, p < 0.05) and calculated glomerular filtration rate (GFR) was decreased (2.68 +/- 1.03 vs. 3.37 +/- 0.11 mL/min, p < 0.05). Intrarenal angiotensin converting enzyme (ACE), angiotensin II (ANG II), angiotensin II type 1 receptor (AT1R) and transforming growth factor-beta (TGF-beta) were upregulated in lead group. Captopril and losartan administration reduced proteinuria significantly (3.0 +/- 0.50 mg/100 g of captopril and 2.7 +/- 0.4 mg/100 g of losartan group) and lowered systolic blood pressure when compared with lead group. Furthermore, serum creatinine levels and GFR were improved by RAS blockade. Captopril treatment significantly reduced protein abundance of ACE, ANG II, AT1R and TGF-beta. Losartan treatment also decreased ANG II and TGF-beta. We concluded that lead exposure elicited intrarenal RAS activation with associated proteinuria and impaired renal function. RAS blockade was effective in alleviating lead-associated kidney injury and lowering blood pressure. (C) 2013 Elsevier Inc. All rights reserved.