Comparison of the natriuretic response to atriopeptin III and loop diuretic in the isolated perfused rat kidney

1. Isolated rat kidneys were perfused at a constant perfusion pressure of 90 mmHg to study the natriuretic effects of atriopeptin III (AP-III) and to compare these effects with those of frusemide. AP-III (1 μg) or frusemide (1 mg) were added to the perfusate (100 ml) after two 15 min control collection periods.

2. Compared with the control group, AP-III and frusemide increased urinary sodium excretion (U_NaV, 5.6 ± 1.1 and 4.6 ± 0.6 vs control 1.8 ± 0.3 μmol min⁻¹ g⁻¹, mean ± sem, P < 0.01 and P < 0.05, respectively), fractional sodium excretion (FE_Na, 4.8 ± 1.1 and 6.7 ± 0.8 vs control 2.0 ± 0.2%, P < 0.05 and P < 0.001, respectively) and potassium excretion (U_KV, 3.2 ± 0.3 and 3.0 ± 0.3 vs control 1.5 ± 0.3 μmol min⁻¹ g⁻¹, both P < 0.01). However, AP-III, but not frusemide, increased glomerular filtration rate (820 ± 55 vs 590 ± 24 μl min⁻¹ g⁻¹, P < 0.01) and urine flow rate (V 97.5 ± 8.0 vs 44.1 ± 5.2 μl min⁻¹ g⁻¹, P < 0.001). Calculated distal delivery of sodium (C_Na + C_H2O, 76.6 ± 6.8 vs 30.7 ± 3.8 μl min⁻¹ g⁻¹, P < 0.005) as well as fractional distal delivery of sodium [(C_Na + C_H2O)/C_In, 9.4 ± 0.9 vs 5.1 ± 0.6%, P < 0.01] were increased by AP-III, but not frusemide. Fractional distal reabsorption of sodium [C_H2O/(C_Na + C_H2O), 51.9 ± 6.5 vs 59.9 ± 2.7%, NS] was not affected by AP-III but was significantly reduced by frusemide (7.4 ± 3.0%, P < 0.001).

3. The natriuretic effects of the combination of AP-III and frusemide were additive even though the distal delivery was no greater than with AP-III alone. These data indicate that AP-III has a unique natriuretic effect different from frusemide, and that the main site of natriuretic action by AP-III is proximal to the ascending loop of Henle. Because of different nephron sites, the effects of AP-III and frusemide are additive, a finding of potential clinical importance.