Protective Effect of Losartan, Non-peptide Angiotensin II Antagonist, on the Course of Postischemic Renal Injury in an Experimental Model

Overview

The effect of non-peptide angiotensin II antagonist losartan (L) on the tolerance of kidneys to warm ischemia was evaluated in a rat model. Ischemiawas induced by temporary closure of renal arteries for 45 minutes. L was administered chronically (CH) via oral route for 4 weeks (10 mg.kg -1 .day -1 ),acutely intravenously before ischemia (A), or after ischemia (B) in the dose 3 mg.kg -1. In the animals of the control group (K) only ischemia of kidneyswas induced. Seven-day survival and the degree of funcional injury of kidneys in rats were assessed according to plasma creatinine and urea levels24 hours after injury.Significantly improved survival was observed only in the CH group compared to K group (92% vs. 62%, P < 0.05). Group A and B were not betterin survival rate compared to K group (60% resp. 64% vs. 62%). We also observed significantly lower creatinine and urea levels 24 hours after ischemiain the group CH compared to group K (166 ± 26 vs. 242 ± 72 mmol/l; 20,3 ± 6,1 vs 47,1 ± 16,7 mmol/l).The study shows that L has protective effect against 45 minutes ischemia in rats only after chronic administration. Acute intravenous administrationimmediately before ischemia or after ischemic injury did not result in renal protection.

Key words:
non-peptide angiotensin II antagonist – losartan – ischemic renal injury – renal graft protection – renal transplantation