Mechanisms underlying renoprotection during renin-angiotensin system blockade

Potential determinants of chronic renal disease (CRD) progression were studied in male Munich-Wistar rats subjected to 5/6 nephrectomy and treated with candesartan (Csn; n = 30) or enalapril (Ena; n = 27) from 5 wk postsurgery. Despite control of systolic blood pressure (SBP; 24 wk: Csn = 143 ± 9; Ena = 148 ± 8 mmHg), urinary protein excretion rates (UprV) increased over 24 wk (Csn = 92 ± 10; Ena = 99 ± 8mg/day). Glomerulosclerosis scores (GS) at 24 wk were similar for Csn (42 ± 7%) vs. Ena (42 ± 4%), values close to those of untreated controls at 12 wk (43 ± 4%). At 24 wk, SBP and UprV correlated strongly with GS, together accounting for 72% of the variance in GS. Renal cortex mRNA levels (determined by competitive RT-PCR) for transforming growth factor (TGF)-β1 and monocyte chemoattractant protein (MCP)-1 were elevated in Csn and Ena at 12 wk and remained higher at 24 wk vs. sham. Strong correlations were evident among TGF-β1, MCP-1, and interleukin-1β and renal injury at 24 wk. Cns and Ena are thus equ...