Evidence That Atrial Natriuretic Factor Is the Humoral Factor by Which Volume Loading or Mannitol Infusion Produces an Improved Renal Function After Acute Ischemia

This experimental study in dogs was designed to investigate whether maximal loading produces atrial natriuretic factor (ANF) release and whether this physiological peptide is involved in the improvement of the early renal function recovery after acute ischemia. The experimental protocol included a renal artery occlusion for 45 min in uninephrectomized dogs and the measurement of various parameters of renal function over 2-hr period after declamping. There were 3 experimental groups. In the control group (I) (n = 10), the dogs received, after ischemia, an isotonic saline solution infusion at a rate of 0.2 ml/kg/min. In group II, (n = 10) the animals underwent acute volemic expansion (1 ml/kg/min) with whole blood (hematocrit approximately equal to 25%) during the ischemic period, and after declamping, an isotonic saline infusion (NaCl 0.9%) infusion at the same rate as in the control group. In group III, (n = 8) the dogs only received NaCl 0.9% (0.2 ml/kg/min) before ischemia and alpha human ANF (3.6 ng/kg/min) dissolved in saline after ischemia and during the 2 hr of the renal recovery period. Volemic expansion induced a highly significant increase of the cardiac filling pressures concomitant with a prompt but transient 5-6-fold increase in ANF levels (357 +/- 92 pg/ml versus 60 +/- 4.1 pg/ml in controls at the time of declamping [P less than 0.05]). With these higher plasma ANF levels in overloaded animals, we observed, 2 hr after declamping, considerably improved renal function recovery in terms of glomerular filtration rate--37.5% +/- 8.7 versus 11.8 +/- 3.9%; urinary sodium excretion rate--53.89 mu eq/min versus 5.36 +/- 1.2 mu eq/min (P less than 0.01); total Na reabsorption rate--1.2 +/- 0.23 meq/min versus 0.28 +/- 0.09 meq/min (P less than 0.01) (group II vs. controls, respectively). A 1-28 alpha ANF infusion after the ischemic insult allowed a comparable but more significant improved recovery of renal function--indeed, 2 hr after declamping, the GFR reached 73.7 +/- 14% of the preoperative GFR values. The urinary sodium excretion rate was 15-fold higher than in controls, and the total and fractional sodium reabsorption rates followed a similar increase. These beneficial effects of ANF were obtained with low doses of synthetic ANF (3.6 ng/kg/min) inducing plasma levels slightly higher (120 pg/ml) than in controls and comparable to the levels reached in the overloading group. In addition, maximal loading or ANF infusion produces an inhibition of the aldosterone rise occurring after the ischemic insult.(ABSTRACT TRUNCATED AT 250 WORDS)