Volume 61, Issue 5, Pages 1635-1645 (May 2002) Effect of combining ACE inhibitor and statin in severe experimental nephropathy  Carla Zoja, Daniela Corna, Daniela Rottoli, Dario Cattaneo, Cristina Zanchi, Susanna Tomasoni, Mauro Abbate, Giuseppe Remuzzi  Kidney International  Volume 61, Issue 5, Pages 1635-1645 (May 2002) DOI: 10.1046/j.1523-1755.2002.00332.x Copyright © 2002 International Society of Nephrology Terms and Conditions

Figure 1 Systolic blood pressure measured at months 4 [(▪) control; () PHN; before treatment] and 10 after disease induction, in PHN rats given vehicle (□), or lisinopril at the doses of 40mg/L (lis 40;) and 400mg/L (lis 400;), or simvastatin (simv;), or the combination of lisinopril 40mg/L plus simvastatin (lis 40 + simv;), and in control rats (▪). Data are mean ± SE. *P < 0.01 vs. control; °P < 0.01 vs. vehicle; §P < 0.01 vs. lisinopril 40 and 400mg/L; #P < 0.01 vs. vehicle and simvastatin; +P < 0.05 vs. control. Kidney International 2002 61, 1635-1645DOI: (10.1046/j.1523-1755.2002.00332.x) Copyright © 2002 International Society of Nephrology Terms and Conditions

Figure 2 Urinary protein excretion measured at months 4 (before treatment) and 10 after disease induction, in PHN rats given vehicle (□), or lisinopril at the doses of 40mg/L (lis 40;) and 400mg/L (lis 400;), or simvastatin (simv;), or the combination of lisinopril 40mg/L plus simvastatin (lis 40 + simv; (), and in control rats (▪). Data are mean ± SE. °P < 0.01 vs. control; *P < 0.05 vs. vehicle and lisinopril 40mg/L. Kidney International 2002 61, 1635-1645DOI: (10.1046/j.1523-1755.2002.00332.x) Copyright © 2002 International Society of Nephrology Terms and Conditions

Figure 3 Serum creatinine levels measured at months 4 [(▪) control; () PHN; before treatment] and 10 after disease induction, in PHN rats given vehicle (□) or lisinopril at the doses of 40mg/L (lis 40;) and 400mg/L (lis 400,), or simvastatin (simv;), or the combination of lisinopril 40mg/L plus simvastatin (lis 40 + simv;) and in control rats. Data are mean ± SE. °P < 0.01 versus control; #P < 0.01 versus other PHN groups. Kidney International 2002 61, 1635-1645DOI: (10.1046/j.1523-1755.2002.00332.x) Copyright © 2002 International Society of Nephrology Terms and Conditions

Figure 4 Linear regression analysis of relationship between proteinuria and serum cholesterol performed at 10 months in PHN and control rats (r = 0.85, P < 0.001). Kidney International 2002 61, 1635-1645DOI: (10.1046/j.1523-1755.2002.00332.x) Copyright © 2002 International Society of Nephrology Terms and Conditions

Figure 5 Renal morphological parameters on biopsies taken at months 4 (before treatment) and 10 after disease induction, in PHN rats given vehicle (□), or lisinopril at the doses of 40mg/L (lis 40;) and 400mg/L (lis 400;), or simvastatin (simv;), or the combination of lisinopril 40mg/L plus simvastatin (lis 40 + simv;) and in control rats (▪). Data are mean ± SE. °P < 0.01 vs. control; #P < 0.01 vs. vehicle and simvastatin; +P < 0.05 vs. lisinopril 40 and 400mg/L; §P < 0.01 vs. vehicle, lisinopril 40 and 400mg/L. Kidney International 2002 61, 1635-1645DOI: (10.1046/j.1523-1755.2002.00332.x) Copyright © 2002 International Society of Nephrology Terms and Conditions

Figure 6 (Top) Renal expression of MCP-1 mRNA assessed at month 10 in age-matched control rats and in PHN rats given vehicle, or lisinopril at the doses of 40mg/L (lis 40) and 400mg/L (lis 400), or simvastatin (simv), or the combination of lisinopril 40mg/L plus simvastatin (lis 40 + simv). Northern blot experiments were performed using total RNA from whole kidney tissue of either separate or pooled samples for each group. Results shown are representative of pooled samples for each group. (Bottom) Densitometric analysis of the autoradiographic signals for MCP-1. Results shown are mean ± SE of separate animals for each group. The optical density of the autoradiographic signals was quantitated and calculated as the ratio of MCP-1 to GAPDH mRNA. Results expressed as fold increase over control (represented as 1) in densitometric arbitrary units. °P < 0.05 vs. control; #P < 0.05 vs. control, vehicle and lisinopril 40mg/L; *P < 0.01 vs. other PHN groups. Kidney International 2002 61, 1635-1645DOI: (10.1046/j.1523-1755.2002.00332.x) Copyright © 2002 International Society of Nephrology Terms and Conditions

Figure 7 Photomicrographs showing MCP-1 mRNA expression by in situ hybridization in kidneys from a control rat (a), a rat with PHN given vehicle (b), and a rat with PHN treated with lisinopril plus simvastatin (c) at 10 months (digoxigenin d-UTP-labeled murine MCP-1 RNA probe, alkaline phosphatase reporter system). (d) Negative control using MCP-1 sense RNA probe in a kidney section of PHN rat plus vehicle adjacent to that shown in panel b (Magnification, ×180). Figure is representative of N = 3 rats examined for each group. Kidney International 2002 61, 1635-1645DOI: (10.1046/j.1523-1755.2002.00332.x) Copyright © 2002 International Society of Nephrology Terms and Conditions