title: Mechanisms of albuminuria in the chronic nitric oxide inhibition model.
abstract: Chronic nitric oxide (NO) inhibition causes hypertension and renal injury. Concomitant salt overload promotes massive albuminuria. We investigated the mechanisms whereby these treatments impair glomerular permselectivity. Adult male Munich-Wistar rats received either a standard-salt (SS; 0.5% Na) or high-salt (HS; 3.1% Na) diet and either no treatment or the NO inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME). At 30 days, albuminuria was moderate, the density of fixed anionic sites at the glomerular basement membrane (GBM), estimated by cationic ferritin binding, declined by approximately 35%, and the fractional clearance of 70-kDa neutral dextran (phi) rose moderately in rats receiving L-NAME and SS. Rats given L-NAME and HS exhibited massive albuminuria, whereas phi was nearly tripled. Depletion of GBM anionic sites was also seen in these rats. The GBM was thickened in both L-NAME-treated groups. These abnormalities were largely reversed after cessation of treatments. These results indicate that chronic L-NAME treatment promotes reversible albuminuria by impairing both glomerular size and charge selectivity. These effects likely reflect functional rather than structural disruption of the glomerular wall.
authors.affiliation: Renal Division, Department of Clinical Medicine, University of São Paulo, Brazil.
authors.forename: M I
authors.initials: MI
authors.lastname: Arcos
authors.forename: C K
authors.initials: CK
authors.lastname: Fujihara
authors.forename: A
authors.initials: A
authors.lastname: Sesso
authors.forename: E B
authors.initials: EB
authors.lastname: de Almeida Prado
authors.forename: M J
authors.initials: MJ
authors.lastname: de Almeida Prado
authors.forename: G
authors.initials: G
authors.lastname: de Nucci
authors.forename: R
authors.initials: R
authors.lastname: Zatz
mesh_terms: D000419:Albuminuria / Q000378:metabolism*; D000818:Animals; D004591:Electrophoresis, Polyacrylamide Gel; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007668:Kidney / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure; D007677:Kidney Function Tests; D007678:Kidney Glomerulus / Q000187:drug effects / Q000648:ultrastructure; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010539:Permeability; D011507:Proteinuria / Q000652:urine; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester