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Effect of Unilateral Ureteral Obstruction and Anti-angiotensin II Treatment on Renal Tubule and Interstitial Cell Apoptosis in Rats

To investigate the effects of angiotensin-converting enzyme inhibitor (cilazapril) and angiotensin II type I receptor antagonist (losartan) on tubular and interstitial cell apoptosis and caspase-3 activity in rats with obstructive nephropathy after unilateral ureteral obstruction. Rats with unilateral obstructive nephropathy and sham-operated rats were treated with cilazapril, losartan, or the vehicle (water). Tubular and interstitial cell apoptosis was detected morphologically on hematoxylin and eosin-stained renal specimens and by the terminal deoxynucleotidyl transferase-mediated nick end-labeling. Caspase-3 activity in whole-kidney tissue homogenates was measured colorimetrically. After unilateral ureter ligation, there was a significant increase in the number of apoptotic tubular and interstitial cells in the obstructed kidney (13.17 ± 8.73 vs. 3.00 ± 4.53 cells per high power field ; P = 0.049 and 6.33 ± 3.27 vs 2.00 ± 2.35 cells per high power field ; P = 0.036, respectively, vs sham-operated rats, 10 days after ligation). In rats with unilateral obstructive nephropathy, neither cilazapril nor losartan had an effect on tubular cell apoptosis. However, cilazapril caused a significant increase in the number of renal apoptotic interstitial cells (7.00 ± 9.74 vs 0.8 ± 1.41 cells per high power field, P = 0.019). Caspase-3 activity was not significantly different in rats with unilateral obstructive nephropathy than in sham-operated rats. Rats with unilateral obstructive nephropathy had increased apoptosis of tubular and interstitial cells in comparison with sham-operated rats. Neither cilazapril nor losartan had an effect on tubular cell apoptosis, and cilazapril even increased interstitial cell apoptosis.

caspase 3; cilazapril; losartan; obstructive nephropathy; TUNEL

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