Renal protective effects of blocking the intrarenal renin-angiotensin system

It has been well demonstrated that angiotensin-converting enzyme inhibitors (ACEIs) can retard the progression of renal failure and kidney sclerosis i n patients and animal models with glomerular diseases. The aim of this stud y was to observe the influences of ACEI on intrarenal Ang II and TGF beta(1 ) local formation and their relation to renal protective effects. Experimen tal glomerulosclerosis with nephrotic syndrome was induced in unilateral ne phrectomized rats with repeated injections of adriamycin. Rats were randoml y divided into three groups: 1) a sham-operated control group (n=8); 2) an NS group treated with ACEI (benazepril 4 mg/kg/d) (n=10), and 3) an NS grou p not treated (n = 10), After 8 wk, serum, urine and renal tissue were coll ected for study. ACE activity and Ang II concentration in renal tissue were measured by colorimetry and radioimmunoassay, respectively. Immunohistoche mistry staining was employed for transforming growth factor-beta(1) (TGF be ta(1)) and extracellular matrix (ECM) examination. TGF beta(1) mRNA was ass essed by in situ hybridization, Compared with those of non-treated nephropa thy rats, ACE activity (13.39+/-5.02 us. 49.13+/-12.92 U/ml, p < 0.01) and Ang II (402.61+/-80.22 us. 751.63+/-137.45 pg/mg/pr p < 0.01) in renal tiss ue were significantly inhibited in the rats treated with ACEI, At the same time, proteinuria was significantly reduced (155.06+/-103.56 us, 421.11+/-1 48.35 mg/24 h, p < 0.01) and renal function improved (Scr 76.3+/-33.1 us, 1 07.1+/-71.0, p < 0.05), concomitant with a reduction in the glomerular scle rosis index (30.6+/-19.5 us. 120.3+/-61.9, p < 0.01) and a reduction in ECM accumulation such as Col IV, III, LN and FN (29.2+/-9.8 vs. 76.8+/-12.3; 2 9.5+/-12.4 vs. 85.9+/-11.5; 26.0+/-5.1 us. 69.6+/-1.73; 32.4+/-12.4 us, 70. 5+/-13.5; p < 0.01 in all cases). In the ACEI treated group, these histolog ic benefits coincided with a reduced expression of TGF beta(1) in both tubu lar cells and sclerosed glomeruli in protein as well as mRNA level. These f indings provide further evidence that ACEI (benazepril) can prevent the pro gression of renal damage in both the function and morphologic changes which associated with a down-regulation of intrarenal Ang II level through the r elative inhibition of renal ACE activity. The blocking of the intrarenal re nin angiotensin system (RAS) might contribute to the inhibition of TGF beta (1) local formation and the TGF beta(1)-mediated ECM accumulation that are related to the renal protective effects of ACEI.