Beneficial effect of the atrial natriuretic factor analog A68828 in postischemic acute renal failure

DM Pollock and TJ Opgenorth

Pharmaceutical Discovery, Abbott Laboratories, Abbott Park, Illinois.

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.

Volume 255, Issue 3, pp. 1166-1169, 12/01/1990
Copyright © 1990 by American Society for Pharmacology and Experimental Therapeutics

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