Beneficial effect of the atrial natriuretic factor analog A68828 in postischemic acute renal failure.
Short-term administration of atrial peptides has been reported to improve renal function in several animal models of acute renal failure. We designed experiments that determined the effect of a 13-amino acid analog of atrial natriuretic factor (ANF), A68828, on renal function in the postischemic model of acute renal failure. Experiments were conducted using euvolemic, male Sprague-Dawley rats (200-250 g) under Inactin anesthesia. Acute renal failure was induced by complete occlusion of both renal arteries for 30 min. After release of the clamp, vehicle (0.1% bovine serum albumin in saline), A68828 (3, 10 or 30 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 micrograms/kg/min) were infused i.v. for a 2-h period. A68828 at 10 micrograms/kg/min produced a significant increase in glomerular filtration rate (GFR) compared with vehicle controls (0.39 +/- 0.08 vs. 0.19 +/- 0.04 ml/min/100 g; P less than .05) despite a lower arterial pressure (87 +/- 5 vs. 101 +/- 5 mm Hg; P less than .05). A subpressor dose of dopamine had no effect on GFR during the postischemic period (0.25 +/- 0.11 ml/min/100 g). Dopamine in combination with A68828 prevented the decrease in arterial pressure seen with A68828 alone but did not potentiate the beneficial effects on GFR (0.28 +/- 0.05 ml/min/100 g). ANF (1-28) at 0.5 micrograms/kg/min increased GFR to levels nearly identical to those induced by A68828 (0.40 +/- 0.04 ml/min/100 g). These results indicate that infusion of a reduced-size analog of ANF improves renal function in the immediate postischemic period. Furthermore, prevention of the hypotensive effects of the analog with dopamine provides no additional beneficial effect.
Pollock
D M
DM
Pharmaceutical Discovery, Abbott Laboratories, Abbott Park, Illinois.
Opgenorth
T J
TJ
D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000209:etiology; D000595:Amino Acid Sequence; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D004298:Dopamine / Q000494:pharmacology; D004359:Drug Therapy, Combination; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007511:Ischemia / Q000150:complications*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000502:physiology; D007684:Kidney Tubules / Q000502:physiology; D008297:Male; D008969:Molecular Sequence Data; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000652:urine; D013997:Time Factors
C066680:A 68828; D009320:Atrial Natriuretic Factor; D012964:Sodium; D004298:Dopamine