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.

Coordinated Contribution of NADPH Oxidase- and Mitochondria-Derived Reactive Oxygen Species in Metabolic Syndrome and Its Implication in Renal Dysfunction

“…CKD patients have oxidative stress, as shown by increased levels of oxidative stress markers, such as MDA and F2-isoprostanes, which further worsen the renal dysfunction ( Tbahriti et al, 2013 ). The major sources of ROS in the kidney are also NADPH oxidases ( Gill and Wilcox, 2006 ; Wan et al, 2016 ; Qaddumi and Jose, 2021 ) and mitochondria ( Plotnikov et al, 2007 ; Lindblom et al, 2015 ).…”

“…NADPH oxidases, NOX1, NOX2, NOX4, and NOX5, are predominantly expressed in renal epithelial, tubulointerstitial, mesangial, and glomerular epithelial cells ( Gill and Wilcox, 2006 ; Zeng et al, 2009 ; Qaddumi and Jose, 2021 ; Yang et al, 2021 ). Metabolic (hyperglycemia, dyslipidemia, ox-LDL, etc.)…”

“…Oxidative stress is also involved in the increased renal vascular resistance in the hypertension in MetS ( Zeng et al, 2009 ; Ando and Fujita, 2012 ; Qaddumi and Jose, 2021 ). Induction of ROS generation in the renal medulla and cortex promotes hypertension ( Cowley et al, 2015 ; Yang et al, 2020 ).…”

“…The chronic administration of Ang II type I receptor (AT 1 R) blocker decreases ROS production and vascular resistance ( Gill and Wilcox, 2006 ; Daenen et al, 2019 ). Both blockade of AT 1 R and stimulation of dopamine receptors are reno-protective against oxidative stress by decreasing NADPH oxidase expression and activity ( Cuevas et al, 2019 ; Daenen et al, 2019 ; Qaddumi and Jose, 2021 ; Yang et al, 2021 ). D 1 R activation increases the expression of the antioxidant, paraoxonase 2, in both lipid and non-lipid rafts in renal proximal tubule cells ( Yang et al, 2015 ), D 2 R decreases ROS production through upregulation of paraoxonase 2 ( Yang et al, 2012 ), DJ-1 ( Cuevas et al, 2012 ), and another antioxidant, sestrin2 ( Yang et al, 2014 ) in the kidney.…”

Dopamine in Health and Disease

“…Qaddumi and Jose [ 2 ] examined the relationship between the dopaminergic system in the kidney, oxidative stress and the regulation of blood pressure. In the kidney, oxidative stress disrupts sodium homeostasis and causes hypertension through vasoconstriction.…”