Renoprotection Provided by Additional Diuretic Treatment in Partially Nephrectomized Ren-2 Transgenic Rats Subjected to the Combined RAS and ETA Blockade

Figures

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  FIGURE 1. The effect of diuretic treatment added to combined RAS and ETA blockade on survival and body weight. Survival rate (A) and body weight (B) in sham-operated TGR (TGR-sham), nephrectomized TGR (TGR-NX) untreated receiving water or treated with the renin-angiotensin system (RAS) blockade alone (TGR-NX + RAS blockade), combined RAS + ETA blockade (TGR-NX + RAS + ETA blockade) or diuretic given with the combined RAS + ETA blockade (TGR-NX + RAS + ETA blockade + diuretic). # P < 0.05 TGR-sham vs. other TGR-NX-treated groups, $ P < 0.05 TGR-NX + RAS treated vs. other TGR-NX-treated groups, @ P < 0.05 TGR-NX + RAS + ETA + diuretic vs. other TGR-NX-treated groups, ∗P < 0.05 untreated TGR-NX group compared with all other treated TGR-NX groups at the same time point.

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  FIGURE 2. The effect of diuretic treatment added to combined RAS and ETA blockade on SBP and cardiac hypertrophy. Systolic blood pressure (A) and cardiac hypertrophy (B) in sham-operated heterozygous Ren-2 transgenic rats (TGR-sham), nephrectomized TGR (TGR-NX) treated with the renin-angiotensin system blockade alone (RAS), combined RAS + ETA blockade (RAS + ETA); or diuretic given with the combined RAS + ETA blockade (RAS + ETA + Diu). # P < 0.05 TGR-sham vs. other TGR-NX-treated groups, Diu – diuretic.

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  FIGURE 3. The effect of diuretic treatment added to combined RAS and ETA blockade on proteinuria and creatinine clearance. Proteinuria (A) and creatinine clearance (B) in sham-operated TGR (TGR-sham), nephrectomized TGR (TGR-NX) untreated receiving water or treated with the renin-angiotensin system (RAS) blockade alone (TGR-NX + RAS), combined RAS + ETA blockade (TGR-NX + RAS + ETA), or diuretic given with the combined RAS + ETA blockade (TGR-NX + RAS + ETA blockade + diuretic). # P < 0.05 TGR-sham vs. other TGR-NX-treated groups, $ P < 0.05 TGR-NX + RAS treated vs. other TGR-NX-treated groups, @ P < 0.05 TGR-NX + RAS + ETA + diuretic vs. other TGR-NX-treated groups, ∗P < 0.05 untreated TGR-NX group compared with all other treated TGR-NX groups at the same time point.

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  FIGURE 4. The effect of diuretic treatment added to combined RAS and ETA blockade on relative kidney weight and glomerular area. Relative kidney weight (A) and glomerular area (B) in sham-operated heterozygous Ren-2 transgenic rats (TGR-sham), nephrectomized TGR (TGR-NX) treated with the renin-angiotensin system blockade alone (RAS), combined RAS + ETA blockade (RAS + ETA); or diuretic given with the combined RAS + ETA blockade (RAS + ETA + Diu). # P < 0.05 TGR-sham vs. other TGR-NX-treated groups, Diu – diuretic. # P < 0.05 TGR-sham vs. other TGR-NX-treated groups, @ P < 0.05 TGR-NX + RAS + ETA + diuretic vs. other TGR-NX-treated groups.

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  FIGURE 5. The effect of diuretic treatment added to combined RAS and ETA blockade on histological markers of renal damage. Glomerulosclerosis index (A) and kidney tubulointerstitial injury (B) in sham-operated heterozygous Ren-2 transgenic rats (TGR-sham), nephrectomized TGR (TGR-NX) treated with the renin-angiotensin system blockade alone (RAS), combined RAS + ETA blockade (RAS + ETA); or diuretic given with the combined RAS + ETA blockade (RAS + ETA + Diu). Diu – diuretic # P < 0.05 TGR-sham vs. other TGR-NX-treated groups, $ P < 0.05 TGR-NX + RAS treated vs. other TGR-NX-treated groups, @ P < 0.05 TGR-NX + RAS + ETA + diuretic vs. other TGR-NX-treated groups.

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  FIGURE 6. Representative images of renal histology. Renal parenchyma without morphological alterations in control sham-operated HanSD rats (HanSD-sham). Extensive secondary focal segmental glomerulosclerosis and small zone of atrophic tubules (the upper right part) in sham-operated heterozygous Ren 2 transgenic rats (TGR-sham). RAS blockade only partially improved morphology of renal parenchyma; focal segmental glomerulosclerosis persists as well as glomerular enlargement in nephrectomized TGR (TGR-NX + RAS). Combined RAS and ETA blockade substantially atenuated renal injury in nephrectomized TGR; glomeruli contain segmental tuft sclerosis only sporadically (TGR-NX + RAS + ETA blockade). Treatment with diuretic added to the combined RAS+ETA blockade most significantly protected renal parenchyma from injury in nephrectomized TGR (TGR-NX + RAS + ETA blockade + diuretic). Periodic acid-Schiff staining. Magnification 200×.