title: Severe proteinuria without impairment of sodium and volume excretion after puromycin aminonucleoside administration in rats.
abstract: The effects of a single intravenous injection of 100 mg/kg puromycin aminonucleoside (PAN) on renal protein, electrolyte, and fluid excretion as well as inulin and lithium clearances in rats were investigated under basal conditions, after iso-oncotic blood volume expansion with bovine serum albumin (BSA) and during infusion of atrial natriuretic peptide (ANP). All treated rats developed severe proteinuria 7-28 days after injection. On day 17, the protein excretion of the PAN group was 1,050 +/- (SE) 118 micrograms/(min x kg body weight) compared with 42.3 +/- 3.9 micrograms/(min x kg body weight) in the control group. Hypoproteinemia, edema or ascites were not observed. The renal protein excretion increased dramatically after BSA infusion and even more during ANP infusion in the PAN group. The PAN-treated animals lost about 62% of the infused BSA during the time of the experiment. No significant changes in protein excretion were observed in the controls. Both groups had similar basal excretions of urine volume, sodium, chloride, and potassium and responded to the BSA and PAN infusions with comparable increases in these parameters. The glomerular filtration rate was slightly, but not significantly higher in the PAN group during the control periods. Increases after BSA and ANP occurred in both groups, reaching significance only in the control group. Proximal tubular function was slightly impaired in PAN-treated rats as judged from a lower increase of the fractional excretion of lithium after BSA. Mean arterial blood pressure was higher in the PAN group (136.2 +/- 2.4 vs. 127.0 +/- 2.2 mm Hg) and fell in both groups to a comparable degree after BSA infusion. A further fall in blood pressure occurred after ANP infusion. Plasma ANP immunoreactivity was not different between the groups and increased after BSA infusion. Our data demonstrate that severe glomerular lesion as indicated by proteinuria can be observed after PAN administration without impairment of distal tubular function as judged from sodium and fluid excretion, and therefore support the view that the sodium retention observed in nephrotic syndrome is due to a separate intrarenal defect rather than a consequence of protein loss.
authors.affiliation: Department of Physiology, University of Toronto, Ont., Canada.
authors.forename: R
authors.initials: R
authors.lastname: Palluk
authors.forename: A T
authors.initials: AT
authors.lastname: Veress
authors.forename: H
authors.initials: H
authors.lastname: Sonnenberg
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D008297:Male; D011507:Proteinuria / Q000139:chemically induced / Q000378:metabolism*; D011691:Puromycin / Q000031:analogs & derivatives*; D011692:Puromycin Aminonucleoside / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D012964:Sodium / Q000652:urine*
chemical_list: D012710:Serum Albumin, Bovine; D011691:Puromycin; D011692:Puromycin Aminonucleoside; D009320:Atrial Natriuretic Factor; D012964:Sodium