Received January 13, 2008
Revised February 8, 2008
Accepted after revision February 18, 2008

¹ University of Virginia

^* To whom correspondence should be addressed. E-mail: hms7a{at}virginia.edu.

	Abstract

Recently, we reported presence of a local renal aldosterone production. In present study we tested the hypothesis that local aldosterone production in the kidney contributes to renal inflammation, matrix formation and albuminuria associated with diabetes. We evaluated changes in renal aldosterone content (RAC), aldosterone synthase expression, nuclear factor B (NFB), tumor necrosis factor (TNF), interleukin-6 (IL-6), transforming growth factor (TGF), glomerular fibronectin, collagen type IV and urine albumin extraction (UAE) in response to aldosterone synthase inhibitor FAD286 (FAD). Studies were conducted in adrenalectomized normoglycemic (control) or diabetic rats for 14 weeks. FAD was administered during the last 10 weeks of the study. Plasma aldosterone levels were not detectable in any of the study groups. Compared to control, diabetic rats had higher levels of RAC by 488% (P < 0.01), NFB by 293% (P<0.01), TNF by 356% (P < 0.01), IL-6 by 378% (P < 0.01), TGF by 337% (P < 0.01), UAE (P < 0.01) and increased glomerular fibronectin and collagen type IV immunostaining. In diabetic rats, FAD reduced RAC (P<0.01), UAE (P<0.05), NFB mRNA, TNF mRNA, IL-6 mRNA and TGF mRNA by 51%, 41%, 41% and 52% and their proteins respectively and decreased glomerular fibronectin, collagen type IV immunostaining. In conclusion, diabetes increases local aldosterone production in the kidney, which contributes to development of renal inflammation, matrix formation and albuminuria. Inhibition of aldosterone production in the kidney could be helpful in management of diabetic nephropathy.

Key Words: Diabetes, Inflammation, Kidney