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2015 ; 165
(4
): 505-11
Nephropedia Template TP
gab.com Text
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English Wikipedia
The renal dopaminergic system: novel diagnostic and therapeutic approaches in
hypertension and kidney disease
#MMPMID25134060
Armando I
; Konkalmatt P
; Felder RA
; Jose PA
Transl Res
2015[Apr]; 165
(4
): 505-11
PMID25134060
show ga
Salt sensitivity of blood pressure, whether in hypertensive or normotensive
subjects, is associated with increased cardiovascular risk and overall mortality.
Salt sensitivity can be treated by reducing NaCl consumption. However, decreasing
salt intake in some may actually increase cardiovascular risk, including an
increase in blood pressure, that is, inverse salt sensitivity. Several genes have
been associated with salt sensitivity and inverse salt sensitivity. Some of these
genes encode proteins expressed in the kidney that are needed to excrete a sodium
load, for example, dopamine receptors and their regulators, G protein-coupled
receptor kinase 4 (GRK4). We review here research in this field that has provided
several translational opportunities, ranging from diagnostic tests to gene
therapy, such as (1) a test in renal proximal tubule cells isolated from the
urine of humans that may determine the salt-sensitive phenotype by analyzing the
recruitment of dopamine D1 receptors to the plasma membrane; (2) the presence of
common GRK4 gene variants that are not only associated with hypertension but may
also be predictive of the response to antihypertensive therapy; (3) genetic
testing for polymorphisms of the dopamine D2 receptor that may be associated with
hypertension and inverse salt sensitivity and may increase the susceptibility to
chronic kidney disease because of loss of the antioxidant and anti-inflammatory
effects of the renal dopamine D2 receptor, and (4) in vivo renal selective
amelioration of renal tubular genetic defects by a gene transfer approach, using
adeno-associated viral vectors introduced to the kidney by retrograde ureteral
infusion.