Prolonged inhibition of angiotensin II attenuates glycerol-induced acute renal failure

1. A lipophilic competitive angiotensin II antagonist (octanoyl-[8-leucine]-angiotensin II, OCTLEU A-II) was used to partially block the renin-angiotensin system in rats with glycerol-induced acute renal failure. The rats, which were maintained either on a normal or on a low-sodium diet, were dehydrated for 24 h before injection of glycerol. Daily intramuscular injections of OCTLEU A-II in peanut oil were started 48 h before glycerol administration to assure an angiotensin II blockade up to 48 h after glycerol administration. 2. In the low-sodium group (N = 23), acute renal failure was significantly attenuated in OCTLEU A-II-treated rats (N = 9) when compared with the controls (N = 14). The following values (means +/- 1 SD) for renal function parameters were obtained for the treated and control groups: urine volume, 15.2 +/- 11.7 vs 1.4 +/- 2.0 ml/24 h (P less than 0.01); plasma creatinine 5.5 +/- 1.3 vs 8.6 +/- 1.3 mg/dl (P less than 0.01); creatinine clearance 0.23 +/- 0.16 vs 0.03 +/- 0.03 ml min-1 kg-1 (P less than 0.01); plasma potassium 6.6 +/- 1.5 vs 10.1 +/- 1.9 mEq/1 (P less than 0.01); and sodium excretion fraction 3.0 +/- 4.0 vs 21.6 +/- 17.4% (P less than 0.02). Mean arterial blood pressure was 107 +/- 23 mmHg for the OCTLEU A-II-treated animals and 102 +/- 18 mmHg for the controls. 3. The rats on a normal sodium diet (N = 16) developed moderate non-oliguric renal insufficiency. The OCTLEU A-II-treated (N = 8) and control (N = 8) groups did not differ in any of the parameters measured. 4. The present results show that sodium restriction aggravates glycerol-induced acute renal failure and that the renin-angiotensin system participates, since its inhibition at the level of the angiotensin II receptor attenuates the extreme loss of renal function and prevents anuria.