Effect of the ANF analog A68828 in cisplatin-induced acute renal failure.
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.
Pollock
D M
DM
Abbott Laboratories, Pharmaceutical Discovery, Abbott Park, Illinois.
Holst
M
M
Opgenorth
T J
TJ
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000188:drug therapy*; D000595:Amino Acid Sequence; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002945:Cisplatin / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008969:Molecular Sequence Data; D009318:Natriuresis / Q000187:drug effects; D011188:Potassium / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects
C066680:A 68828; D009320:Atrial Natriuretic Factor; D002945:Cisplatin; D011188:Potassium