Blunted excretory response to atrial natriuretic peptide in experimental nephrosis

Abstract

Adriamycin (ADR) nephrosis and a model of unilateral ADR-induced proteinuria were produced in Sprague-Dawley (S.D.) rats to investigate the mechanism of sodium retention by the nephrotic kidney. Plasma volume, as measured by the dilution principle using radioiodinated serum albumin, was significantly higher in nephrotic animals than in control ones (NS: 69.61 ± 15.02: control: 47.05 ± 5.32 ml/kg: P < 0.01). Similarly plasma levels of immunoreactive ANP (iANP) were significantly higher in nephrotic animals compared to controls (NS 104.22 ± 36.41; control 59.94 ± 20.88 pg/ml; P < 0.05). Using the unilateral model we found a markedly reduced diuretic and natriuretic response to the infusion of synthetic rat atrial natriuretic peptide (ANP 1-28) in proteinureic kidney but not in contralateral kidney, despite a comparable increase in glomerular filtration rate. To explain the blunted diuresis and natriuresis in the presence of normal glomerular response to ANP, we investigated the possibility of an abnormality at post-glomerular level by studying ANP receptor density and affinity of the inner stripe of outer medulla and the inner medulla in ADR- and vehicle-treated rats. The inner stripe of outer medulla and the inner medulla receptor density and affinity were not significantly different in ADR rats as compared to animals given the vehicle alone. These results show that: 1) plasma volume and plasma levels of iANP are significantly higher in ADR-treated rats as compared to control animals; 2) the reduced diuretic and natriuretic response to synthetic ANP in the unilateral model of ADR nephrosis is a consequence of an abnormal response of the proteinuric kidney and does not reflect systemic changes; and 3) the inner stripe of outer medulla and the inner medulla ANP receptor density and affinity are comparable in normal and nephrotic rats.