The effects of atrial natriuretic factor (ANF) were evaluated in rats with chronic aorto-caval (A-V) fistula. In this experimental model of high-output heart failure, the animals display elevated atrial pressure and systemic vasodilation, but avidly retain sodium. Experiments were performed on Munich-Wistar rats, 8 to 14 days after placement of an infrarenal surgical anastomosis (side-to-side, 0.9 ± 0.2 mm) and on sham operated controls. Infusion of synthetic ANF (3-28) intravenously (5 μg/kg prime; 0.17 μg/kg.min) resulted in increases in urine flow (V) and fractional sodium excretion (FE(Na)) and decreases in blood pressure (BP) that were significantly attenuated in rats with A-V fistula compared to controls. To control for the lower baseline BP that was present in rats with A-V fistula, a second series of studies was performed in which renal perfusion pressure was reduced in normal rats to 110 mm Hg with a servocontrolled pneumatic cuff. ANF infusion to this group led to significant increases in glomerular filtration rate (GFR), V and FE(Na) that were greater than those seen in rats with A-V fistula (FE(Na) = 2.7 ± 0.3% vs. 0.48 ± 0.12%, P < 0.05). Thus, the moderately reduced BP in rats with A-V fistula did not account for the blunted response to ANF. To investigate whether the renal sensitivity to ANF is altered in this model, an additional series of experiments were performed in which ANF was infused over a range of doses (0.08 to 2.5 μg/kg.min) to both groups of rats. The changes in BP, GFR, V and FE(Na) following the incremental doses of ANF were significantly attenuated in rats with A-V fistula. Indeed, the maximum natriuresis in rats with A-V fistula was significantly lower in rats with A-V fistula compared to controls (FE(Na) = 2.1 ± 0.7% vs. 5.0 ± 0.5%, P < 0.05). These data indicate that rats with A-V fistula have a diminished sensitivity to ANF infusion. The blunted natriuretic response to ANF may contribute to the renal retention of sodium in this experimental model of heart failure.
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