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.