Effect of atrial natriuretic factor on renal function in rats with nephrotic syndrome

This study was designed to evaluate the renal effects of atrial natriuretic factor [ANF(8-33)] in rats with aminonucleoside (AMN)-induced nephrotic syndrome. AMN (100 mg/kg iv) was administered to adult female rats either 2 (AMN 2, n = 7), 4 (AMN 4, n = 7), 6 (AMN 6, n = 7), or 14 (AMN 14, n = 6) days before clearance experiments; untreated (UNT, n = 7) animals served as controls. During clearance experiments, rats were anesthetized with pentobarbital sodium. Protein excretion rates were similar between UNT and AMN 2 but increased stepwise in AMN 4, AMN 6, and AMN 14 rats. The glomerular filtration rate (GFR) was similar in UNT and AMN 2, lower in AMN 4 and AMN 14, and lowest in AMN 6 rats. Basal sodium excretion (UNaV) was not different among the five groups. An ANF primer (1.0 micrograms/kg iv) plus a constant infusion (0.1 micrograms.kg-1.min-1) for 1 h produced a significantly lower increase in UNaV in AMN 2 and AMN 14 than in UNT and was not natriuretic or diuretic in AMN 4 or AMN 6 rats. The ANF-induced increase in UNaV was similar between AMN 2 and AMN 14 rats. ANF had no effect on the GFR in any group. A higher ANF bolus (5.0 micrograms/kg iv) was then infused. This ANF bolus increased UNaV only in UNT and AMN 2 rats. Finally, a bolus of furosemide (4.0 mg/kg iv) was given; UNaV increased similarly in UNT, AMN 2, and AMN 14, and to a lesser extent in AMN 4 and AMN 6 rats. Thus, there is an attenuated natriuretic and diuretic response to ANF in rats with AMN-induced nephrotic syndrome. This altered responsiveness to ANF may contribute to the sodium and water retention characteristic of this disorder.