In vitro and in vivo protective effect of atriopeptin III on ischemic acute renal failure

Abstract

The effect of atriopeptin III (AP-III) on ameliorate ischemic acute renal failure was first examined in the isolated perfused kidney. Isolated rat kidneys were clamped for 1 h and reperfused for 30 min without therapy and then perfused with either 0 (control) or 100 μg/dl AP-III. In this system AP-III significantly improved renal plasma flow (39.6 ± 2.4 vs. 32.2 ± 2.1 ml/min per g; P < 0.05) inulin clearance (182.6 ± 49.2 vs. 24.6 ± 6.2 μl/min per g; P < 0.05), urine flow (52.9 ± 12.1 vs. 7.1 ± 0.8 μl/min per g, P < 0.01), and net tubular sodium reabsorption (21.2 ± 6.6 vs. 2.9 ± 0.9 μmol/min per g, P < 0.05) as compared with control. A second series of in vivo studies experiments were performed using 1 h of bilateral renal artery clamping followed by an intravenous infusion of either saline alone (control) or AP-III (0.20 μg/kg per min) for 60 min. The results demonstrated that inulin clearance (244.4 ± 25.1 vs. 15.8 ± 8.2 μl/min per 100 g; P < 0.01), urine flow (23.1 ± 5.9 vs. 1.1 ± 0.5 μl/min per 100 g; P < 0.01), and net tubular sodium reabsorption (38.9 ± 4.7 vs. 4.3 ± 1.6 μmol/min per 100 g; P < 0.01) were significantly higher in AP-III-treated rats than controls during the hour of AP-III infusion. In 1 h posttreatment study this significant protective effect of AP-III was documented to persist. In more chronic studies animals treated acutely with AP-III had lower serum creatinine concentration at 24 h (1.8 ± 0.3 vs. 3.3 ± 0.4 mg/dl; P < 0.01) and 48 h (1.0 ± 0.2 vs. 2.4 ± 0.4 mg/dl; P < 0.01) after the 60 min of ischemia than controls. Renal adenosine triphosphate regeneration as assessed by P-31 nuclear magnetic resonance during reflow was also significantly improved in AP-III-treated animals at 1 h (3.03 ± 0.30 vs. 1.45 ± 0.40 μmol/g dry wt; P < 0.05) and 2 h (3.98 ± 0.46 vs. 1.80 ± 0.05 μmol/g dry wt; P < 0.01) of reflow as compared with control rats. Thus, AP-III significantly ameliorates ischemic acute renal failure both in vitro and in vivo in the rat.