The Role of the Renal Dopaminergic System and Oxidative Stress in the Pathogenesis of Hypertension

Abstract

The kidney is critical in the long-term regulation of blood pressure. Oxidative stress is one of the many factors that is accountable for the development of hypertension. The five dopamine receptor subtypes (D₁R-D₅R) have important roles in the regulation of blood pressure through several mechanisms, such as inhibition of oxidative stress. Dopamine receptors, including those expressed in the kidney, reduce oxidative stress by inhibiting the expression or action of receptors that increase oxidative stress. In addition, dopamine receptors stimulate the expression or action of receptors that decrease oxidative stress. This article examines the importance and relationship between the renal dopaminergic system and oxidative stress in the regulation of renal sodium handling and blood pressure. It discusses the current information on renal dopamine receptor-mediated antioxidative network, which includes the production of reactive oxygen species and abnormalities of renal dopamine receptors. Recognizing the mechanisms by which renal dopamine receptors regulate oxidative stress and their degree of influence on the pathogenesis of hypertension would further advance the understanding of the pathophysiology of hypertension.

Keywords: blood pressure; dopamine; dopamine receptor; dopaminergic system; hypertension; kidney; oxidative stress.

Figure 1

Schematic diagram summarizing dopamine receptor subtypes. Gα_S, G_S alpha subunit; Gα_i/Gα_o, G_i alpha subunit/G_o alpha subunit; AC, Adenylyl Cyclase; cAMP, Cyclic Adenosine Monophosphate.

Figure 2

Diagram displaying the distribution of dopamine receptor subtypes (D₁R-D₅R) along the parts of a nephron. OS: outer stripe; IS: inner stripe; S₁: first segment of the proximal tubule [121].

Figure 3

Schematic diagram displaying the role of renal D₂R and interrelated components on the development of hypertension. The dashed lines illustrate inhibitory effects and solid lines illustrate stimulatory effects. D₂R, Dopamine D₂ Receptor; D₂R SNPs, Dopamine D₂ Receptor Single Nucleotide Polymorphisms; DJ-1, Park 7; HO-2, Heme-Oxygenase-2; NOX, NADPH oxidase; PON2, Paraoxonase 2.

Figure 4

Schematic diagram displaying the role of renal D₅R and interrelated components on the development of hypertension. The dashed lines illustrate inhibitory effects and solid lines illustrate stimulatory effects. D₅R, Dopamine D₅ Receptor; PON2, Paraoxonase 2; HO-1, Heme Oxygenase-1; PLD2, Phospholipase D2; PKC, Protein Kinase C.