Experiments were conducted to determine the effects of the reduced-size
atrial natriuretic factor (
ANF) analog,
A68828, on renal function in rats with
cisplatin (CP)-induced
acute renal failure. CP was given as a single
intraperitoneal injection (7.5 mg/kg) 3 days before experiments. In separate groups of rats, the renal response to
intravenous infusion of
A68828 at 3, 10 or 30 micrograms/kg/min or
ANF[1-28] at 0.03, 0.1 or 0.3 micrograms/kg/min for 2 hr was evaluated. Another group of CP-treated rats were infused with the vehicle (0.1%
bovine serum albumin in
0.9% NaCl). CP treatment resulted in a marked decline in glomerular filtration rate (GFR), arterial pressure, heart rate and reabsorption of water and
electrolytes compared to untreated control animals. Infusion of
A68828 produced a dose-dependent improvement in the glomerular filtration rate. The highest dose of
A68828 produced a nearly 3-fold increase in the glomerular filtration rate, whereas arterial pressure was decreased; heart rate was unchanged. Despite producing a significant diuresis and natriuresis, net tubular reabsorption of water and
sodium was also increased. Similar dose-dependent effects were observed with the native
peptide,
ANF[1-28]. These data indicate that infusion of the reduced-sized analog of
ANF,
A68828, can significantly improve glomerular and tubular function in rats with
acute renal failure induced by CP.