title: Renal dopamine receptors, oxidative stress, and hypertension.
abstract: Dopamine, which is synthesized in the kidney, independent of renal nerves, plays an important role in the regulation of fluid and electrolyte balance and systemic blood pressure. Lack of any of the five dopamine receptor subtypes (D1R, D2R, D3R, D4R, and D5R) results in hypertension. D1R, D2R, and D5R have been reported to be important in the maintenance of a normal redox balance. In the kidney, the antioxidant effects of these receptors are caused by direct and indirect inhibition of pro-oxidant enzymes, specifically, nicotinamide adenine dinucleotide phosphate, reduced form (NADPH) oxidase, and stimulation of anti-oxidant enzymes, which can also indirectly inhibit NADPH oxidase activity. Thus, stimulation of the D2R increases the expression of endogenous anti-oxidants, such as Parkinson protein 7 (PARK7 or DJ-1), paraoxonase 2 (PON2), and heme oxygenase 2 (HO-2), all of which can inhibit NADPH oxidase activity. The D5R decreases NADPH oxidase activity, via the inhibition of phospholipase D2, and increases the expression of HO-1, another antioxidant. D1R inhibits NADPH oxidase activity via protein kinase A and protein kinase C cross-talk. In this review, we provide an overview of the protective roles of a specific dopamine receptor subtype on renal oxidative stress, the different mechanisms involved in this effect, and the role of oxidative stress and impairment of dopamine receptor function in the hypertension that arises from the genetic ablation of a specific dopamine receptor gene in mice.
authors.affiliation: Department of Medicine, Division of Nephrology, University of Maryland School of Medicine, Baltimore, MD 21201-1599, USA. scuevas@medicine.umaryland.edu
authors.forename: Santiago
authors.initials: S
authors.lastname: Cuevas
authors.forename: Van Anthony
authors.initials: VA
authors.lastname: Villar
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Jose
authors.forename: Ines
authors.initials: I
authors.lastname: Armando
mesh_terms: D000818:Animals; D006801:Humans; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D007668:Kidney / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D011954:Receptors, Dopamine