Salt-loaded, spontaneously hypertensive
stroke-prone rats show progressive increases in blood pressure and
proteinuria and accumulate
acute-phase proteins in body fluids, modeling events during renal damage. The aim of this study was to assess the pathological events occurring in the kidney of spontaneously hypertensive
stroke-prone rats over time and evaluate the effects of
statin treatment, which is known to improve renal and cardiovascular outcomes. Kidneys of male spontaneously hypertensive
stroke-prone rats euthanized at different stages of
proteinuria showed progressive inflammatory cell infiltration, the accumulation of alpha-smooth muscle actin-positive cells, degenerative changes in podocytes, and severe
fibrosis. These were accompanied by an imbalance in the
plasminogen/
plasmin and
metalloprotease systems characterized by the increased renal expression of
plasminogen activator inhibitor-1,
tissue plasminogen activator, and
urokinase plasminogen activator; the net result was an increase in
plasmin and
matrix metalloproteinase (MMP)-2 and a reduction in MMP-9 activity. Chronic treatment with the hydrophilic
rosuvastatin had renoprotective effects in terms of morphology and
inflammation and prevented the changes in
plasmin, MMP-2, and MMP-9 activity. These effects were independent of the changes in blood pressure and plasma
lipid levels. Treatment with the lipophilic
simvastatin was not renoprotective. These data suggest that
rosuvastatin may have potential utility as a therapeutic option in renal diseases that are characterized by
inflammation and
fibrosis.