ATRIAL-NATRIURETIC-PEPTIDE AND DOPAMINE IN ESTABLISHED ACUTE-RENAL-FAILURE IN THE RAT

Recent studies have shown that atrial natriuretic peptide (ANP) alone or combined with dopamine (D) markedly improved renal function when given immediately after an ischemic insult. However, the potential beneficial effect of ANP or ANP-D in the established phase of acute renal failure (ARF) and the duration of this effect have not been examined. In the present study atriopeptin III (APIII) and D, sufficient to maintain mean arterial pressure between 100 and 110 mm Hg, or normal saline were given i.v. for four hours to awake Munich-Wistar rats (N = 6 each group) two days after ARF induction with intrarenal norepinephrine (NE). Renal function and morphology were then examined two days after treatment (Day 4). Serum creatinine (S(Cr)) was similarly increased in both groups at the time of APIII-D or saline infusion (Day 2). By Day 4 S(Cr) had decreased to the pre-ARF induction level in APIII-D-treated rats (P < 0.005), but continued to rise in saline-treated animals (P < 0.025). Day 4 renal blood flow and glomerular filtration rate (GFR) were higher in APIII-D-compared to the saline-treated group (9.13 +/- 1.14 vs. 4.41 +/- 2.25 ml/min and 0.787 +/- 0.066 vs. 0.370 +/- 0.185 ml/min, respectively, both P < 0.005). Single nephron GFR was higher in APIII-D-treated rats (96 +/- 47 vs. 37 +/- 28 ml/min, P < 0.025) primarily due to an increase in glomerular capillary pressure (51 +/- 4 vs. 43 +/- 5 mm Hg, P < 0.02). Urine flow rate and fractional excretion of sodium were less in APIII-D-treated rats (P < 0.05). While comparison of percent abnormal tubular profiles for specific kidney zones showed little difference between the two groups, the overall sums of percent abnormal profiles for all zones demonstrated significantly less tubular necrosis (P < 0.001) and tubular regeneration (P < 0.025) and fewer tubular casts (P < 0.01) in the kidneys of APIII-D-treated rats. It is concluded that APIII-D not only increases GFR in the established phase of ARF, but the effect is sustained. While the major effect of APIII-D may be to increase SNGFR in at least a sufficient number of nephrons to impact on whole kidney filtration rate, there also appears to be an effect on restoration of tubular function and morphology.