Natriuretic and diuretic effects of infusion of atrial natriuretic factor in conscious dogs

We studied the effects of 30-min infusions of the synthetic 25-amino acid atrial natriuretic factor [ANF-(102-126)] and the 28-amino acid ANF-(99-126)] at 0.1 and 0.3 μg · kg^-1 · min^-1 on urine flow rate, sodium excretion, and arterial pressure in conscious dogs. Each dose was administered on a separate day following a 1-h stabilization period. We also compared the effects of 60-min infusions of ANF, 0.01 μg · kg^-1 · min^-1, or water infusion on separate days in conscious dogs. Arterial pressure was reduced in a dose-dependent fashion, reaching statistical significance at a dose of 0.3 μg · kg^-1 · min^-1. During the 0.01-μg · kg^-1 · min^-1 infusion, the plasma concentration of ANF rose approximately threefold (from 68 ± 7 to 207 ± 14 pg/ml), with no change in urine flow rate, sodium excretion, or arterial pressure. At a dose of 0.1 μg · kg^-1 · min^-1, urine flow increased (P < 0.05) by 0.41 ± 0.15 ml/min, and sodium excretion rose by 72 ± 24 μeq/min, but not significantly, whereas plasma ANF levels rose to 1,236 ± 229 pg/ml. At the highest dose of ANF (0.3 μg · kg^-1 · min^-1) urine flow rose by 0.62 ± 0.16 ml/min, P < 0.05, and sodium excretion rose by 139 ± 30 μeq/min, P < 0.05, whereas plasma levels of ANF rose to 2,436 ± 320 pg/ml. In contrast, volume loading with dextran increased urine flow by 3.5 ± 1.3 ml/min, P < 0.05, and sodium excretion by 439 ± 147 μeq/min, P < 0.05, whereas ANF rose to only 320 ± 69 pg/ml. These results suggest that, in the conscious dog, ANF does not cause significant diuretic or natriuretic effects until plasma levels are markedly above those observed in physiological conditions. A possible explanation for the difference between this and previous studies is that the renal effects of ANF, at physiological plasma levels, are indirect and thus dependent on autonomic and hormonal (angiotensin, vasopressin, and aldosterone levels) factors governing the renal function of the animal.