Glomerular Basement Membrane Polyanionic Sites and Nitric Oxide in Genetically Salt-Sensitive and Resistant Hypertensive Rats

Abstract

Cationic colloid gold, a polycationic histochemical probe, was used to analyze the distribution of glomerular basement membrane (GBM) polyanions, including heparan sulfate protoglycan in genetic salt-sensitive (SBH/Y) and resistant (SBN/Y) hypertensive rats, with or without high dietary salt intake. GBM morphology, renal function and nitric oxide, as measured by plasma and urine nitrite (NO₂) and nitrate (NO₃) were also determined. In the salt-sensitive rats the high-salt dietary intake resulted in severe hypertension, proteinuria and decreased glomerular filtration rate. After 1 month of high-salt intake, the average width of the GBM of salt-sensitive rats was higher by 27% than that of salt-resistant rats. The number of GBM anionic sites (lamina rata externa and interna) was much lower in both salt-sensitive and salt-resistant groups after 1 month of salt loading, 8.04 ± 0.36 and 7.8 ± 0.25 counts/cm, respectively, compared to the respective values of non-salt-loaded animals, 20.58 ± 1.08 counts/cm in the SBH/Y (p < 0.001) and 21 ± 1.86 counts/cm in the SBN/Y (p < 0.001). A decreased nitric oxide production was found in the salt-sensitive rats before and after salt loading compared with the salt-resistant group. No correlation was found between the nitric oxide changes and the GBM modifications. It is concluded that high-salt intake may be deleterious to the permselectivity of the GBM. It is suggested that salt restriction in hypertension may have a beneficial effect in preventing GBM permselectivity changes and proteinuria.

Proteinuria and glomerulosclerosis in the Sabra genetic rat model of salt susceptibility

“…Salt loading, but not salt susceptibility per se, has been claimed to predispose the kidney to injury, for example, by rendering the kidneys more susceptible to angiotensin II-induced injury (16). We have previously shown in the Sabra rat that high salt intake is deleterious to the permselectivity of the glomerular basement membrane and that 1 mo of salt loading was sufficient to reduce the number of anionic sites in the lamina rara externa and interna (15). However, since we observed differential susceptibility to renal injury without salt loading in SBH/y and SBN/y, these mechanisms do not appear to play a role under these circumstances.…”

Glomerular Basement Membrane Anionic Sites in Adriamycin Nephropathy: Effect of Saline Loading and Nitric Oxide Modulation

“…We found a similar effect of salt loading in genetically hypertension salt-sensitive rats [24]and SHR [unpubl. data].…”

“…In a recent study [24]we found that chronic saline loading in rats is associated with similar alteration in the GBM functional size barrier. It may be hypothesized that saline loading in ADR nephropathy will result in a more severe GBM damage.…”