Effect of atrial natriuretic factor on renal cGMP production in rats with adriamycin-induced nephrotic syndrome.

Adriamycin-induced nephrotic syndrome in the rat is associated with a blunted natriuretic response to infusion of atrial natriuretic factor. To study the mechanism of renal hyporesponsiveness to the peptide in rats with experimental nephrosis, we evaluated the effects of the hormone on renal production of cGMP, the second messenger of the hormone. Baseline GFR and sodium excretion were lower in nephrotic as compared with normal controls. Infusion of synthetic rat atrial natriuretic factor (10 micrograms/kg/h) increased fractional sodium excretion by 7.3 +/- 2.4% in control rats but only by 1.4 +/- 0.5% in adriamycin-treated rats (P less than 0.05). However, the increments in urinary nucleotide excretion rate (UcGMP x V/GFR), in response to atrial natriuretic factor infusion, were comparable in control and nephrotic rats (control, 114.7 +/- 16.1 pmol/mL; adriamycin, 95.5 +/- 12.0 pmol/mL; P was not significant). The in vitro generation of cGMP in response to incremental doses of the hormone (10(-11) to 10(-6) M + 1 mM 3-isobutyl methyl xanthine) was of similar magnitude in isolated glomeruli derived from control (2.4 +/- 0.25 to 9.1 +/- 1.0 pmol/mg of protein) and nephrotic rats (2.9 +/- 0.2 to 10.3 +/- 1.0 pmol/mg of protein) and was not impaired in suspensions of medullary tissue derived from nephrotic rats (control, 8.4 +/- 0.6 to 14.2 +/- 1.2 pmol/mg of protein; adriamycin, 7.3 +/- 0.7 to 22.0 +/- 2.4 pmol/mg of protein).(ABSTRACT TRUNCATED AT 250 WORDS)