Renal dopaminergic system: Pathophysiological implications and clinical perspectives

Table 1 Renal dopaminergic system impairment in experimental hypertension

Animal experimental model	Renal dopaminergic system impairment	Principal findings	Ref.
Spontaneously hypertensive rats	D1-like receptor function impairment caused by a defective coupling of the receptor with AC	Increased sodium reabsorption as a mechanism of hypertension	Ohbu et al[61]
Dahl salt-sensitive rats	D1-like receptor function impairment caused by a defective coupling of the receptor with AC	Prehypertensive Dahl salt-sensitive rats exhibit a blunted natriuretic response to dopamine compared with Dahl salt-resistant rats	Nishi et al[62]
DOCA salt-sensitive rats	Decreased renal dopamine production	Renal dopaminergic system is dominantly supressed in this model of hypertension	Iimura et al[63]
Dopamine receptor knockout mice	Defective D1-D2 like receptor/signal transduction	Impaired D1 and D2-like receptor signal pathway associated with development of hypertension	Banday et al[64] Zeng et al[65] Albrecht et al[66]
C57BL/6 mice	D1-like receptor function impairment associated with increased expression of GRK4 upon salt loading	Impaired ability to excrete a salt load with a resultant increase in blood pressure levels	Escano et al[67]
Mice with selective proximal tubule AADC deletion	Deletion of the kidney’s ability to generate dopamine is associated with unbuffered response to angiotensin II that leads to hypertension and decreased longevity in mice	Increased expression of tubular sodium transporters, decreased natriuresis and diuresis in response to L-Dopa, decreased medullary COX-2 expression and urinary prostaglandin E2 excretion, increased renin and AT1 receptor expression, decreased AT2 and Mas receptor expression, and finally salt-sensitive hypertension.	Zhang et al[42]
Old FBN rats	Reduction of G-protein coupling in response to D1R activation associated with exaggerated AT1 receptor activity	Increase of oxidative stress	Chugh et al[68]
Renalase knockout mice	Alteration of urinary dopamine concentration in luminal fluid and proximal tubular transport	Impaired sodium excretion with increased blood pressure	Desir[18]
3/4 nephrectomized (3/4nx) rats	Decrease in urinary levels of dopamine and in renal AADC activity	A reduction in the natriuretic response to volume expansion with a time-dependent increase in both systolic and diastolic blood pressure	Moreira-Rodrigues et al[69]
Obese Zucker rats	Decrease in D1-like dopamine receptor binding sites and diminished activation of G proteins	Overproduction of ROS	Hussain et al[70]

GRK4: G protein receptor kinase 4; D1R: Dopamine receptor subtype 1; COX-2: Cyclooxygenase type 2; AT1: Angiotensin II receptor subtype 1; AT2: Angiotensin II receptor subtype 2; ROS: Reactive oxygen species; AC: Adenylate cyclase; FBN: Fischer 344 x Brown Norway F1.