Aldosterone Receptor Blockade Prevents Inflammatory Reaction on Type 2 Diabetic Nephropathy / 대한신장학회잡지

ABSTRACT

BACKGROUND: Aldosterone induces renal injury independent of angiotensin II. This harmful effect might be mediated via inflammatory reaction. Aldosterone receptor blockade can retard renal damage in various renal diseases including diabetic nephropathy. However, it is not clear which mechanism is related to the beneficial effect of aldosterone receptor blockade in diabetic nephropathy. Therefore, we investigated whether aldosterone receptor blockade, spironolactone, inhibited inflammatory changes in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type 2 diabetes. METHODS: To determine the inflammatory effects, urinary MCP-1 protein was measured by ELISA, and intrarenal MCP-1 mRNA and ED-1 expression were examined by RT-PCR and immunohistochemistry, respectively. RESULTS: Blood glucose concentration were higher in diabetic rats than in control rats. Urinary protein excretion was significantly higher in diabetic rats compared with controls since twenty weeks, and proteinuria of the diabetic rats was decreased by spironolactone treatment. Urinary excretion of monocyte chemoattractant peptide-1 (MCP-1) was rapidly increased at the early period in diabetic rats. Spironolactone suppressed urinary level of MCP-1 compared to untreated diabetic rats. Immunohistochemistry revealed a significant increase in ED-1 staining in the diabetic kidney, and spironolactone treatment significantly suppressed intrarenal ED-1 expression in diabetic rats. CONCLUSION: Aldosterone receptor blockade, spironolactone, suppressed proteinuria and inflammatory changes in diabetic rats. These results suggest that spironolactone may have an anti-inflammatory effect in diabetic nephropathy.