Table 1.

Summary of Renal Dopamine Receptors, Oxidative Stress, and Hypertension

Receptor subtype	Effects of renal dopamine receptors on the physiological status	Functional deficits in hypertension	Manifestation in gene knockout/knockdown mice or gene mutant	References
D1R	Inhibits renal sodium transport; induces natriuresis and diuresis; disperses NOX subunits, decreases NADPH oxidase expression and activity; interacts with antioxidant enzymes such as PON2.	Decreased D1R-mediated natriuresis and diuresis in SHR and Dahl salt-sensitive rats; impaired D1R-mediated inhibition of sodium transport in hypertensive subjects; reduced D1R expression in obese Zucker rats; increased renal NADPH oxidase expression and activity in hypertensive rats and subjects.	Increased blood pressure after selective inhibition of the renal dopamine subtype D1R with AS-ODN in conscious SD rats; reduced urinary sodium excretion and urine output and elevated blood pressure in Drd1−/− mice.	(4, 15, 23, 63, 77, 88, 107, 108, 133, 156, 162, 173, 184)
D5R	Inhibits renal sodium transport; induces natriuresis and diuresis; inhibits NADPH oxidase expression and activity; increases PON2 expression.	Decreased D5R expression in RPT cells and renal brush border membranes of SHR; impaired D5R internalization and trafficking in salt-induced hypertension.	Elevated blood pressure, and increased expression of renal sodium transporters in Drd5−/− mice; enhanced systemic oxidative stress in Drd5−/− mice; increased renal PLD activity, NADPH oxidase expression and activity, decreased renal expression of PON2 and HO-1 protein, and impaired HO activity in Drd5−/− mice; increased blood pressure and renal NADPH oxidase activity, and decreased urine sodium excretion in hD5R173F>L transgenic mice.	(13, 73, 87, 92b, 151, 154, 158, 173, 176, 177, 193)
D2R	Inhibits noradrenaline release from the kidney; modulates renal local dopamine synthesis; limits renal inflammation; inhibits renal NKA activity in the presence of D1-like receptors; decreases hyperoxidized peroxiredoxins and reduces ROS production, accompanied with decreased NOX4 expression and NADPH oxidase activity; interacts with antioxidant enzymes, including PON2, DJ-1, and sestrin2.	Decreased D2R expression in obese Zucker rats.	Hypertension associated with salt sensitivity, and sodium retention in Drd2−/− mice; increased renal ROS production, NADPH oxidase expression and activity, and renal inflammation in Drd2−/− mice; renal inflammation and fibrosis induced by D2R SNPs (rs6276, rs6277, and rs1800497).	(8, 36, 61, 74, 79, 81, 84, 109, 122, 145, 156, 174, 175, 196)
D3R	Induces natriuresis and diuresis; inhibits renal NHE and NKA activity; modulates renal hemodynamics and tubular function, and increases amino acid-induced glomerular hyperfiltration.	Decreased renal D3R expression in the cortex and RPT cells of SHR; impaired D3R-imediated diuresis and natriuresis in SHR; impaired inhibition of sodium transport in SHRs and in hypertensive Dahl salt-sensitive rats.	Hypertension and decreased urine flow rate and sodium excretion in Drd3−/− mice.	(7, 12, 93–95, 113, 114, 131, 155, 172, 187, 188)
D4R	Inhibits vasopressin-dependent transepithelial Na+ transport and osmotic water permeability; inhibits NKA activity.	Impaired D4R-imediated NKA inhibiton in RPT cells of SHR; decreased D4R expression in obese Zucker rats.	Hypertension associated with increased renal AT1R expression in Drd4−/− mice.	(24, 138, 140, 156)

AS-ODN, antisense oligodeoxynucleotide; AT₁R, angiotensin II type 1 receptor; D₁R, dopamine D₁ receptor; D₂R, dopamine D₂ receptor; D₃R, dopamine D₃ receptor; D₄R, dopamine D₄ receptor; D₅R, dopamine D₅ receptor; HO-1, heme oxygenase-1; NADPH, nicotinamide-adenine dinucleotide phosphate; NHE, sodium hydrogen exchanger; NKA, Na⁺-K⁺-ATPase; PLD, phospholipase D; PON2, paraoxonase 2; ROS, reactive oxygen species; RPT, renal proximal tubule; SD, Sprague-Dawley; SHR, spontaneously hypertensive rat; SNP, single-nucleotide polymorphism.