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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 micrograms/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 less than 0.05) inulin clearance (182.6 +/- 49.2 vs. 24.6 +/- 6.2 microliters/min per g; P less than 0.05), urine flow (52.9 +/- 12.1 vs. 7.1 +/- 0.8 microliters/min per g, P less than 0.01), and net tubular sodium reabsorption (21.2 +/- 6.6 vs. 2.9 +/- 0.9 mumol/min per g, P less than 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 microgram/kg per min) for 60 min. The results demonstrated that inulin clearance (244.4 +/- 25.1 vs. 15.8 +/- 8.2 microliters/min per 100 g; P less than 0.01), urine flow (23.1 +/- 5.9 vs. 1.1 +/- 0.5 microliters/min per 100 g; P less than 0.01), and net tubular sodium reabsorption (38.9 +/- 4.7 vs. 4.3 +/- 1.6 mumol/min per 100 g; P less than 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 less than 0.01) and 48 (1.0 +/- 0.2 vs. 2.4 +/- 4.0 mg/dl; P less than 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 mumol/g dry wt; P less than 0.05) and 2 h (3.98 +/- 0.46 vs. 1.80 +/- 0.05 mumol/g dry wt; P less than 0.01) or reflow as compared with control rats. Thus, AP-III significantly ameliorates ischemic acute renal failure both in vitro and in vivo in the rat.

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