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Agents that interfere with the renin-angiotensin system (RAS) may ameliorate progressive renal injury, particularly in a setting where intrarenal RAS activity appears to be elevated. Whether RAS antagonists affect renal disease progression when intrarenal RAS activity is not increased is unclear. In this study, therefore, the effects of the angiotensin II receptor antagonist losartan on glomerular and tubulointerstitial injury were investigated in obese Zucker rats (OZR), an experimental model of progressive renal disease characterized by reduced intrarenal renin content and reduced plasma renin activity. Losartan (100 or 200 mg/L of drinking water) was administered to OZR beginning at 26 wk of age, when renal disease was established. At 38 and 44 wk of age, losartan-treated OZR demonstrated significant (P   0.05). Similarly, the tubulointerstitial injury score (range, 0 to 4) in the three groups was, respectively, 1.7 +/- 0.4, 1.6 +/- 0.3, and 1.5 +/- 0.3 (P &gt; 0.05). It was concluded that in a setting of chronic renal failure where intrarenal RAS activity does not appear to be increased, angiotensin II receptor antagonism may not be nephroprotective despite a reduction in blood pressure.

The angiotensin II receptor antagonist losartan reduces blood pressure but not renal injury in obese Zucker rats.