Renoprotective effect of pravastatin in salt-loaded Dahl salt-sensitive rats.

The pathophysiological features of nephrosclerosis may be analogous to those of atherosclerosis, which is intimately related to lipid metabolism. Thus, we examined whether a lipid-lowering agent, pravastatin, would ameliorate renal damage in hypertensive model animals. Salt-loaded Dahl salt-sensitive (S) rats were given pravastatin (2 mg/ml in drinking water) for 5 weeks. Pravastatin decreased systolic blood pressure. Although pravastatin did not influence the serum total, high-density, or low-density lipoprotein cholesterol, serum triglycerides were decreased. Pravastatin decreased urinary protein excretion and ameliorated histopathological damage in salt-loaded Dahl S rats. Increased urinary excretion of 8-iso-prostagaldin F2alpha and 8-hydroxy-2'-deoxyguanosine and renal superoxide overproduction and decreased reduced glutathione in the renal parenchyma were ameliorated with pravastatin in Dahl S rats fed a high salt diet. Therefore, pravastatin inhibited the progression of renal injury in salt-loaded Dahl S rats, through its antioxidant as well as its depressor effects.