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 (P=0.049 and 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 (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.