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

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.