Korean J Nephrol.
2005 Sep;24(5):691-698.
Aldosterone Receptor Blockade Prevents Inflammatory Reaction on Type 2 Diabetic Nephropathy
- Affiliations
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- 1Department of Internal Medicine, College of Medicine, Inje University, Korea.
- 2Department of Pathology, College of Medicine, Inje University, Korea.
- 3Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea. cdragn@unitel.co.kr
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.
Keyword
MeSH Terms
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Aldosterone*
Angiotensin II
Animals
Blood Glucose
Diabetic Nephropathies*
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry
Inflammation
Kidney
Monocytes
Proteinuria
Rats
Receptors, Mineralocorticoid*
RNA, Messenger
Spironolactone
Aldosterone
Angiotensin II
Blood Glucose
RNA, Messenger
Receptors, Mineralocorticoid
Spironolactone
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