Intrarenal dopamine deficiency leads to hypertension and decreased longevity in
Authors Zhang MZ, Yao B, Wang S, Fan X, Wu G, Yang H, Yin H, Yang S, Harris RC
Submitted By Raymond Harris on 8/1/2012
Status Published
Journal The Journal of clinical investigation
Year 2011
Date Published 7/1/2011
Volume : Pages 121 : 2845 - 2854
PubMed Reference 21701066
Abstract In addition to its role as an essential neurotransmitter, dopamine serves
important physiologic functions in organs such as the kidney. Although the
kidney synthesizes dopamine through the actions of aromatic amino acid
decarboxylase (AADC) in the proximal tubule, previous studies have not
discriminated between the roles of extrarenal and intrarenal dopamine in the
overall regulation of renal function. To address this issue, we generated mice
with selective deletion of AADC in the kidney proximal tubules (referred to
herein as ptAadc-/- mice), which led to selective decreases in kidney and
urinary dopamine. The ptAadc-/- mice exhibited increased expression of nephron
sodium transporters, decreased natriuresis and diuresis in response to
l-dihydroxyphenylalanine, and decreased medullary COX-2 expression and urinary
prostaglandin E2 excretion and developed salt-sensitive hypertension. They had
increased renin expression and altered renal Ang II receptor (AT) expression,
with increased AT1b and decreased AT2 and Mas expression, associated with
increased renal injury in response to Ang II. They also exhibited a
substantially shorter life span compared with that of wild-type mice. These
results demonstrate the importance of the intrarenal dopaminergic system in salt
and water homeostasis and blood pressure control. Decreasing intrarenal dopamine
subjects the kidney to unbuffered responses to Ang II and results in the
development of hypertension and a dramatic decrease in longevity.

Investigators with authorship
Raymond HarrisVanderbilt University