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.