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.