Mechanisms of albuminuria in the chronic nitric oxide inhibition model

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. Adu lt 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 mem brane (GBM), estimated by cationic ferritin binding, declined by similar to 35%, and the fractional clearance of 70-kDa neutral dextran (phi) rose mod erately in rats receiving L-NAME and SS. Rats given L-NAME and HS exhibited massive albuminuria, whereas phi was nearly tripled. Depletion of GBM anio nic 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 promote s reversible albuminuria by impairing both glomerular size and charge selec tivity. These effects likely reflect functional rather than structural disr uption of the glomerular wall.