Blunted excretory response to atrial natriuretic peptide in experimental nephrosis.
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 less than 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 less than 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 proteinuric 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Perico
N
N
Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
Delaini
F
F
Lupini
C
C
Benigni
A
A
Galbusera
M
M
Boccardo
P
P
Remuzzi
G
G
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000502:physiology*; D001798:Blood Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D004317:Doxorubicin; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007672:Kidney Cortex / Q000648:ultrastructure; D008297:Male; D009404:Nephrotic Syndrome / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D010953:Plasma Volume / Q000187:drug effects; D011507:Proteinuria / Q000139:chemically induced; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D017461:Receptors, Atrial Natriuretic Factor; D011956:Receptors, Cell Surface / Q000378:metabolism; D012964:Sodium / Q000378:metabolism
D001798:Blood Proteins; D011956:Receptors, Cell Surface; D004317:Doxorubicin; D009320:Atrial Natriuretic Factor; D012964:Sodium; D017461:Receptors, Atrial Natriuretic Factor