Local delivery of angiotensin receptor blocker into the kidney ameliorates progression of experimental glomerulonephritis  J. Mahmood, F. Khan, S. Okada, N. Kumagai, T. Morioka, T. Oite  Kidney International  Volume 70, Issue 9, Pages 1591-1598 (November 2006) DOI: 10.1038/sj.ki.5001872 Copyright © 2006 International Society of Nephrology Terms and Conditions

Figure 1 Urinary protein excretion in Nx and Nx+ATS rats. Urinary protein excretion in rats was determined in 24h urinary specimens 9 and 14 days after injection of 1-22-3 Ab. Data are expressed as mean values±s.d.; ##P<0.01 vs Nx rats at day 9, **P<0.01 at day 9 vs Nx+ATS and ¶¶P<0.01 vs Nx+ATS at day 14. (N=12). Kidney International 2006 70, 1591-1598DOI: (10.1038/sj.ki.5001872) Copyright © 2006 International Society of Nephrology Terms and Conditions

Figure 2 Immunofluorescent staining in Nx+ATS rats for AT1 receptors at day 14. (a) Disease control group (Nx+ATS), (b) Nx+ATS+ARB group, (c) Nx+ATS+Ang II group, (d) Nx+ATS+Ang II+ARB group, and (e) Nx group (original magnification × 400). Kidney International 2006 70, 1591-1598DOI: (10.1038/sj.ki.5001872) Copyright © 2006 International Society of Nephrology Terms and Conditions

Figure 3 Immunofluorescent double staining in Nx+ATS rat for endothelial cells (PECAM-1) and renin cells (renin Ab) at day 14. (a) Nx+ATS, (b) Nx+ATS+Ang II group, (c) Nx+ATS+Ang II+ARB group, (d) Nx+ATS+ARB group. FITC-labeled renin expression was only observed in the Nx+ATS+ARB-treated group (original magnification × 400). Kidney International 2006 70, 1591-1598DOI: (10.1038/sj.ki.5001872) Copyright © 2006 International Society of Nephrology Terms and Conditions

Figure 4 Light microscopic findings in anti-Thy-1.1 nephritis rats (Nx+ATS) Rats at day 14. (b) In the Nx+ATS+Ang II group, there was thickening of glomerular basement membrane with severe, diffuse mesangiolytic changes. Some glomeruli showed crescentic lesions with increased production of extracellular matrix. (c) In the Nx+ATS+Ang II+ARB group and (a) Nx+ATS group, glomerular lesions were relatively less severe compared to the Nx+ATS+Ang II group. (d) In the Nx+ATS+ARB group, remarkably mild mesangial sclerotic lesions with significantly decreased mesangial cell proliferation were observed compared to all other groups (bar=50μm). Kidney International 2006 70, 1591-1598DOI: (10.1038/sj.ki.5001872) Copyright © 2006 International Society of Nephrology Terms and Conditions

Figure 5 ARB treatment improved glomerular expansion in Nx+ATS rats at 14 day. Data are expressed as mean values±s.d. (N=12). **P<0.01 vs disease control group. Kidney International 2006 70, 1591-1598DOI: (10.1038/sj.ki.5001872) Copyright © 2006 International Society of Nephrology Terms and Conditions

Figure 6 ARB treatment improved sclerotic indexes in Nx+ATS rats at 14 day. Data are expressed as mean values±s.d. (N=12). **P<0.01 vs disease control group. Kidney International 2006 70, 1591-1598DOI: (10.1038/sj.ki.5001872) Copyright © 2006 International Society of Nephrology Terms and Conditions

Figure 7 Light microscopic findings at day 14 in uninephrectomized (Nx) rats. (a) Nx group, (b) Nx+Ang II, (c) Nx+Ang II+ARB group, (d) Nx+ARB (bar=50μm). Kidney International 2006 70, 1591-1598DOI: (10.1038/sj.ki.5001872) Copyright © 2006 International Society of Nephrology Terms and Conditions

Figure 8 mRNA expression of Ang II receptors (AT1a, AT1b, and AT2) in Nx+ATS rats at day 14 by real-time PCR. The results are shown as ratios to the mRNA expression of GAPDH. Data are expressed as mean values±s.d. **P<0.01 vs disease control group. Kidney International 2006 70, 1591-1598DOI: (10.1038/sj.ki.5001872) Copyright © 2006 International Society of Nephrology Terms and Conditions

Figure 9 RBC velocity within the glomeruli in Nx+ATS group at day 9. Nine days after the disease induction the RBC velocity in Nx+ATS+Ang II group was significantly reduced, but when combined with Nx+ATS+ARB the velocity increased, as in the Nx+ATS group. There was a significantly increased intraglomerular erythrocyte velocity in the Nx+ATS+ARB group compared to all other groups. All data were expressed as means±s.d. **P<0.01 vs disease control group (N=12). Kidney International 2006 70, 1591-1598DOI: (10.1038/sj.ki.5001872) Copyright © 2006 International Society of Nephrology Terms and Conditions