Renoprotective effect of angiotensin II receptor antagonists in experimental chronic renal failure

We compared the antihypertensive and renoprotective effects of the angioten sin II receptor antagonist losartan and the calcium channel blocker verapam il in the rat with chronic renal failure. One month after five-sixths nephr ectomy, male WKY rats were treated for 2 months with either losartan or ver apamil. Both resulted in a similar reduction in blood pressure: from 147.1 to 112 mm Hg in losartan-treated and from 155 to 118 mm Hg (p = NS) in vera pamil-treated rats. Losartan improved the creatinine clearance (difference +17.1% as compared with +6.6% for verapamil, p = 0.039) and prevented the i ncrease in proteinuria: 12.26 +/- (SE) 2.33 mg/day before and 18.48 +/- 2.1 9 mg/day (p = NS) after therapy in the losartan-treated and 17.27 +/- 2.73 mg/day before and 32.27 +/- 10.29 mg/day after therapy (p = 0.0484) in the verapamil-treated group. In addition, losartan resulted in minimal mesangia l proliferation and significantly less glomerular sclerosis and thickening of the small arterial and arteriolar walls. The changes in interstitial fib rosis and tubular hypertrophy, however, were similar in both the verapamil- and losartan-treated groups. Treatment with losartan 1 month after five-si xths nephrectomy in male WKY rats resulted in reduced blood pressure, simil ar to that of the verapamil-treated group. However, despite similar antihyp ertensive properties, losartan improved creatinine clearance and reduced pr oteinuria. The losartan-treated group also had a marked reduction in mesang ial proliferation and less glomerular sclerosis and less reduced vascular w all thickness in renal small arteries and arterioles. However, losartan did not totally eliminate nephrosclerosis. The tubular and interstitial change s were fewer in the losartan-treated group. Thus losartan has an additional , although only partial, renoprotective effect when compared with verapamil . Copyright (C) 2001 S. Karger AG,Basel.