The effect of 1-sarcosine, 8-leucyl angiotensin II on glycerol-induced acute renal failure.

Several studies have suggested that increased activity of the renin-angiotensin system plays an important role in the pathogenesis of acute renal failure. An analog of angiotensin II, 1-sarcosine, 8-leucyl angiotensin II (AIIA), a potent antagonist of the pressor response of angiotensin II (AII), was injected (16 mug/200 gm) or infused (1.5 mug/200 gm/min) intravenously into glycerol treated (8 ml/kg) rats to evaluate the involvement of the renin-angiotensin system as a mediator in the pathogenesis of acute renal failure. Dehydrated animals, whether untreated, given AIIA, or saline became progressively azotemic and died with 72 hours after glycerol administration. Plasma renin activity, as measured by radioimmunoassay, decreased below dehydrated control levels at one hour after glycerol administration (7.45 ng/ml/hr +/- 1.29 (SE) to 3.24 +/- 0.64), and progressively increased to a maximum 9.9 +/- 0.98) at 17 hours; there was no difference between dehydrated control levels and those obtained 24 and 48 hours after glycerol. Nondehydrated glycerol treated rats were studied as above. These animals developed a non-lethal form of acute renal failure, the severity of which was also unaffected by AIIA administration. These observations indicate that AIIA neither prevents nor alters the development of glycerol induced acute renal failure.