Intrarenal dopamine inhibits progression of diabetic nephropathy.
Authors Zhang MZ, Yao B, Yang S, Yang H, Wang S, Fan X, Yin H, Fogo AB, Moeckel GW,
Harris RC
Submitted By Raymond Harris on 1/30/2013
Status Published
Journal Diabetes
Year 2012
Date Published 10/1/2012
Volume : Pages 61 : 2575 - 2584
PubMed Reference 22688335
Abstract The kidney has a local intrarenal dopaminergic system, and in the kidney,
dopamine modulates renal hemodynamics, inhibits salt and fluid reabsorption,
antagonizes the renin-angiotensin system, and inhibits oxidative stress. The
current study examined the effects of alterations in the intrarenal dopaminergic
system on kidney structure and function in models of type 1 diabetes. We studied
catechol-O-methyl-transferase (COMT)(-/-) mice, which have increased renal
dopamine production due to decreased dopamine metabolism, and renal
transplantation was used to determine whether the effects seen with COMT
deficiency were kidney-specific. To determine the effects of selective
inhibition of intrarenal dopamine production, we used mice with proximal tubule
deletion of aromatic amino acid decarboxylase (ptAADC(-/-)). Compared with
wild-type diabetic mice, COMT(-/-) mice had decreased hyperfiltration, decreased
macula densa cyclooxygenase-2 expression, decreased albuminuria, decreased
glomerulopathy, and inhibition of expression of markers of inflammation,
oxidative stress, and fibrosis. These differences were also seen in diabetic
mice with a transplanted kidney from COMT(-/-) mice. In contrast, diabetic
ptAADC(-/-) mice had increased nephropathy. Our study demonstrates an important
role of the intrarenal dopaminergic system to modulate the development and
progression of diabetic kidney injury and indicate that the decreased renal
dopamine production may have important consequences in the underlying
pathogenesis of diabetic nephropathy.

Investigators with authorship
Raymond HarrisVanderbilt University

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