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We investigated the hemodynamic responses to three doses of atrial natriuretic factor [human atrial natriuretic factor-(99-126)] (ANF) in nephrectomized rabbits anesthetized with ketamine and acepromazine. The influence of the different doses of the peptide on the hemodynamic consequences produced by acute volume expansion (0.9% NaCl, 1.4 ml/kg/min for 60 minutes) was also studied. All three dosages of ANF (0.001, 0.01, and 0.2 micrograms/kg/min for 20 minutes) significantly reduced blood pressure. With the lowest dose, the hypotensive effect was associated with reduction in systemic vascular resistance and no significant change in heart rate, stroke volume, central venous pressure, and hematocrit. In contrast, the intermediate and high doses, which resulted in markedly higher plasma levels, caused a significant decrease in heart rate, central venous pressure, and stroke volume; a slight rise in hematocrit; and no change in systemic vascular resistance. Volume expansion produced by saline infusion in an additional group of nephrectomized rabbits increased central venous pressure and decreased hematocrit. When ANF infusion was associated to volume expansion, each dosage of ANF was able to reduce the rise in central venous pressure, while only the higher dosage attenuated the progressive fall in hematocrit caused by volume expansion. Plasma volume, measured at the end of volume expansion was lower in the group treated with the highest dose of ANF than in the control animals (28.2 +/- 9 vs. 35.1 +/- 3 ml/kg, p less than 0.05). We conclude that 1) ANF induces significant hemodynamic effects independently from its renal action.(ABSTRACT TRUNCATED AT 250 WORDS)

We investigated the influence of acute volume expansion on the hemodynamic and renal responses to the constant infusion of atrial natriuretic factor (ANF) (alpha-human ANP, 2 micrograms/kg bolus, 0.2 microgram.kg-1.min-1) in rabbits anesthetized with ketamine and acepromazine. The effects of the peptide were evaluated in 12 euvolemic rabbits and in 15 rabbits during the steady-state phase of volume expansion (0.9% NaCl 4.5 ml/min for 60 min). In the euvolemic animals, ANF caused an increase in natriuresis and a reduction in blood pressure (BP), which was associated with a decrease in cardiac output (CO), stroke volume (SV), and no significant changes in central venous pressure (CVP), peripheral hematocrit (Hct), and heart rate (HR). When the peptide was infused in the volume-expanded animals, the effects of ANF on BP and HR were comparable with those observed in the euvolemic animals. However, in these animals the ANF-induced changes in CO, SV, CVP, and Hct were significantly greater than those observed in the euvolemic group. In addition, the percent increases in diuresis and natriuresis were significantly smaller than those obtained in the euvolemic animals. In conclusion, volume expansion with saline potentiates the effects of ANF on systemic hemodynamics and blood volume.