Beneficial Effect of the ANF Analog A68828 on Recovery from Ischemic Acute Renal Failure

Abstract

We have recently reported that administration of the ANF analog A68828 improves renal function in an acute model of postischemic acute renal failure. The current investigation examined the question whether a short-term infusion of A68828 can attenuate the long-term decrement in renal function following an ischemic event. Acute renal failure was induced in male Sprague-Dawley rats (200-250 g) by complete occlusion of both renal arteries for 30 min. During the initial 60 min following ischemia, vehicle (0.1% BSA in saline), A68828 (10 micrograms/kg/min); dopamine (10 micrograms/kg/min); A68828 (10 micrograms/kg/min) plus dopamine (10 micrograms/kg/min); or ANF[1-28] (0.5 microgram/kg/min) were infused intravenously. In vehicle-treated animals, a very large increase in plasma creatinine was observed, with peak levels at 2 days postischemia (5.5 +/- 1.2 mg/dL). A68828 alone, A68828 with dopamine, or ANF[1-28] infusion attenuated the rise in plasma creatinine levels by approximately 50% on each day of the study; dopamine alone was no different from vehicle-treated controls. Gross histological examination of kidneys on the fourth day postischemia revealed that significantly less damage occurred only in the group treated with A68828 alone. These results indicate that infusion of a reduced-size analog of ANF for a brief period in the postischemic kidney improves renal function and lessens tissue damage as evaluated several days after the ischemic event. Furthermore, dopamine infusion provides no discernable beneficial effect.