Inhibition of the renal renin-angiotensin system and renoprotection by pitavastatin in type1 diabetes.

1. The aim of the present study was to investigate whether or not pitavastatin ameliorates diabetic nephropathy and if inhibition of the rennin-angiotensin-aldosterone system (RAAS) is associated with any renoprotective effects. Pitavastatin (10mg/ kg/day) and/or spironolactone (100mg/kg/day) were given by gavage for 3weeks to uninephrectomized rats with streptozotocin-induced diabetes.

Spironolactone exhibits direct renoprotective effects and inhibits renal renin-angiotensin-aldosterone system in diabetic rats.

Aldosterone itself has been reported to participate in mediating renal injury, and it was confirmed that the aldosterone synthase CYP11B2 gene, protein, and aldosterone production are locally present in the kidney. To test the hypothesis that a mineralocorticoid receptor antagonist might ameliorate diabetic nephropathy and the inhibition of renal CYP11B2 expression might be associated with these renoprotective effects, spironolactone (50 mg/kg/day) was administered by gavage to uninephrectomized diabetic rats for 3 weeks. Streptozotocin (55 mg/kg, i.