The Role of Dopamine D2 receptors and Oxidative Stress in the Pathogenesis of Hypertension

Main Article Content

Chunyu Zeng Jian Yang Robin A Felder Ines Armando Pedro A. Jose

Abstract

Globally, hypertension is the number one risk factor for death, affecting more than 1 billion people. Hypertension is the result of the interactions among genetics, epigenetics, environment, and lifestyle. The long-term regulation of blood pressure rests on renal and non-renal mechanisms. The impaired renal sodium handling in hypertension is caused by aberrant counter-regulatory natriuretic/anti-natriuretic pathways. The sympathetic nervous and renin-angiotensin systems are anti-natriuretic pathways. A counter-regulatory natriuretic pathway is the renal dopaminergic system. Aberrant dopaminergic regulation of renal sodium transport in hypertension is caused by a decrease in renal dopamine synthesis and/or dysfunction of any of the 5 dopamine receptors (D1R, D2R, D3R, D4R, & D5R). Normally, an increase in sodium intake increases while a decrease in sodium intake decreases blood pressure, albeit transiently until sodium balance is achieved. However, ~50 % of hypertensive and ~26% of normotensive subjects have increased blood pressure on high sodium intake, a case of salt sensitivity, while ~20 % have increased blood pressure on a low sodium intake, a case of inverse salt sensitivity. Low and high sodium intakes are associated with increased incidence of cardiovascular events/mortality. In humans with inverse salt sensitivity, there is a linear relationship between the number of single nucleotide polymorphisms in DRD2 (rs6276 and 6277) and decreased renal D2R expression. The increase in blood pressure on a low sodium diet may be due to increased activities of the renin-angiotensin and sympathetic nervous systems that cannot be counteracted by D2R. Hypertension may be a cause or consequence of inflammation or oxidative stress. Deficient D2R function causes renal inflammation independently of the increase in blood pressure. Subjects carrying DRD2 single nucleotide polymorphisms have increased inflammation, mediated by decreased regulation of the miR-217-Wnt5a-Ror2 pathway. The D2R, via paraoxonase2 and sestrin2, maintains normal redox balance and blood pressure. In summary, the D2R is important in the maintenance of normal blood pressure by regulating renal sodium transport, vascular reactivity, inflammation, and redox balance.

Article Details

How to Cite
ZENG, Chunyu et al. The Role of Dopamine D2 receptors and Oxidative Stress in the Pathogenesis of Hypertension. Medical Research Archives, [S.l.], v. 12, n. 4, apr. 2024. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/5150>. Date accessed: 27 may 2024. doi: https://doi.org/10.18103/mra.v12i4.5150.
Section
Research Articles

References

1. https://world-heart-federation.org/what-we-do/hypertension/

2. Centers for Disease Control and Prevention, National Center for Health Statistics. National Vital Statistics System, Mortality 2018-2021 on CDC WONDER Online Database, released in 2023. Data are from the Multiple Cause of Death Files, 2018-2021, as compiled from data provided by the 57 vital statistics jurisdictions through the Vital Statistics Cooperative Program. Accessed at
http://wonder.cdc.gov/mcd-icd10-expanded.html on Aug 7, 2023, 12:25:01 PM

3. Heron M. Deaths: Leading Causes for 2019. Natl Vital Stat Rep. 2021;70(9):1-114.

4. Hall JE, Granger JP, do Carmo JM, et al. Hypertension: physiology and pathophysiology. Compr Physiol. 2012;2(4):2393-2442. doi: 10.1002/cphy.c110058.

5. Jung MH, Ihm SH. Obesity-related hypertension and chronic kidney disease: from evaluation to management. Kidney Res Clin Pract. 2023;42(4):431-444. doi: 10.23876/j.krcp.23.072.

6. Drury ER, Wu J, Gigliotti JC, Le TH. Sex Differences in Blood Pressure Regulation and Hypertension: Renal, Hemodynamic, and Hormonal Mechanisms. Physiol Rev. Physiol Rev. 2024;104(1):199-251.
doi: 10.1152/physrev.00041.2022.

7. Hahad O, Rajagopalan S, Lelieveld J, et al. Noise and Air Pollution as Risk Factors for Hypertension: Part II-Pathophysiologic Insight. Hypertension. 2023;80(7):1384-1392. doi: 10.1161/HYPERTENSIONAHA.123.20617

8. Yin Y, Yu Z, Wang J, Sun J. Effects of the different Tai Chi exercise cycles on patients with essential hypertension: A systematic review and meta-analysis. Front Cardiovasc Med. 2023;10:1016629.
doi: 10.3389/fcvm.2023.1016629.

9. Wattanapisit A, Ng CJ, Angkurawaranon C, Wattanapisit S, Chaovalit S, Stoutenberg M. Summary and application of the WHO 2020 physical activity guidelines for patients with essential hypertension in primary care. Heliyon. 2022;8(10):e11259. doi: 10.1016/j.heliyon.2022.e11259

10. Kokubo Y, Padmanabhan S, Iwashima Y, Yamagishi K, Goto A. Gene and environmental interactions according to the components of lifestyle modifications in hypertension guidelines. Environ Health Prev Med. 2019;24(1):19. doi: 10.1186/s12199-019-0771-2.

11. Nierenberg JL, Li C, He J, et al. Blood Pressure Genetic Risk Score Predicts Blood Pressure Responses to Dietary Sodium and Potassium: The GenSalt Study (Genetic Epidemiology Network of Salt Sensitivity). Hypertension. 2017;70(6):1106-1112. doi: 10.1161/HYPERTENSIONAHA.117.10108.

12. Osazuwa-Peters OL, Waken RJ, Schwander KL, et al. Identifying blood pressure loci whose effects are modulated by multiple lifestyle exposures. Genet Epidemiol. 2020;44(6):629-641. doi: 10.1002/gepi.22292.

13. Sun X, Pan Y, Zhang R, et al. Life-Course Associations between Blood Pressure-Related Polygenic Risk Scores and Hypertension in the Bogalusa Heart Study. Genes (Basel). 2022;13 (8):1473. doi: 10.3390/genes13081473.

14. Arnett DK, Claas SA. Omics of Blood Pressure and Hypertension. Circ Res. 2018; 122(10):1409-1419.
doi: 10.1161/CIRCRESAHA.118.311342

15. Wuttke M, Li Y, Li M, Sieber KB, et al. A catalog of genetic loci associated with kidney function from analyses of a million individuals. Nat Genet. 2019;51(6):957-972. doi: 10.1038/s41588-019-0407-x.

16. Pérez-Gimeno G, Seral-Cortes M, Sabroso- Lasa S, et al. Development of a genetic risk score to predict the risk of hypertension in European adolescents from the HELENA study. Front Cardiovasc Med. 2023;10:1118919.

17. Kurniansyah N, Goodman MO, Khan TK, et al. Evaluating the use of blood pressure polygenic risk scores across race/ethnic background groups. Nat Commun. 2023;14 (1):3202. doi: 10.3389/fcvm.2023.1118919.

18. Du B, Jia X, Tian W, et al. Associations of SUCNR1, GRK4, CAMK1D gene polymorphisms and the susceptibility of type 2 diabetes mellitus and essential hypertension in a northern Chinese Han population. J Diabetes Complications. 2021;35(1):107752. doi: 10.1016/j.jdiacomp.2020.107752.

19. Cipolletta E, Ciccarelli M, Izzo R, Finelli R, Trimarco B, Iaccarino G. A polymorphism within the promoter of the dopamine receptor D1 (DRD1 -48A/G) associates with impaired kidney function in white hypertensive patients. Transl Med UniSa. 2012;2:10-19.

20. Giri A, Hellwege JN, Keaton JM, et al. Trans-ethnic association study of blood pressure determinants in over 750,000 individuals. Nat Genet. 2019;51(1):51-62. doi: 10.1038/s41588-018-0303-9.

21. Davenport AP, Hyndman KA, Dhaun N, et al. Endothelin. Pharmacol Rev. 2016;68(2): 357-418. doi: 10.1124/pr.115.011833.

22. Albrecht FE, Drago J, Felder RA, et al. Role of the D1A dopamine receptor in the pathogenesis of genetic hypertension. J Clin Invest. 1996;97(10):2283-2288. doi: 10.1172/JCI118670.

23. Felder RA, Sanada H, Xu J, et al. G protein- coupled receptor kinase 4 gene variants in human essential hypertension. Proc Natl Acad Sci USA. 2002;99(6):3872-3877. doi: 10.1073/pnas.062694599.

24. Zhang MZ, Yao B, Wang S, et al. Intrarenal dopamine deficiency leads to hypertension and decreased longevity in mice. J Clin Invest. 2011;121(7):2845-2854. doi: 10.1172/JCI57324.

25. Carey RM, Schoeffel CD, Gildea JJ, et al. Salt sensitivity of blood pressure is associated with polymorphisms in the sodium-bicarbonate cotransporter. Hypertension. 2012;60(5):1359- 1366.
doi: 10.1161/HYPERTENSIONAHA.112.196071.

26. Titze J, Rakova N, Kopp C, Dahlmann A, Jantsch J, Luft FC. Balancing wobbles in the body sodium. Nephrol Dial Transplant. 2016; 31(7):1078-1081. doi: 10.1093/ndt/gfv343.

27. Laurent S, Boutouyrie P. The structural factor of hypertension: large and small artery alterations. Circ Res. 2015;116(6):1007-1021. doi: 10.1161/CIRCRESAHA.116.303596.

28. Dinh Cat AN, Friederich-Persson M, White A, Touyz RM. Adipocytes, aldosterone and obesity-related hypertension. J Mol Endocrinol. 2016;57(1):F7-21. doi: 10.1530/JME-16-0025.

29. Joyner MJ, Limberg JK. Blood pressure: return of the sympathetics? Curr Hypertens Rep. 2016;18(1):7. doi: 10.1007/s11906-015-0616-3.

30. Grassi G, Dell'Oro R, Quarti-Trevano F, Vanoli J, Oparil S. Sympathetic Neural Mechanisms in Hypertension: Recent Insights. Curr Hypertens Rep. 2023;25(10):263-270. doi: 10.1007/s11906-023-01254-4.

31. Cao W, Yang Z, Liu X, et al. A kidney-brain neural circuit drives progressive kidney damage and heart failure. Signal Transduct Target Ther. 2023;8(1):184. doi: 10.1038/s41392-023-01402-x.

32. Kosaki K, Park J, Matsui M, et al. Elevated urinary angiotensinogen excretion links central and renal hemodynamic alterations. Sci Rep. 2023;13(1):11518. doi: 10.1038/s41598-023-38507-w.

33. Yamaguchi H, Gomez RA, Sequeira-Lopez MLS. Renin Cells, From Vascular Development to Blood Pressure Sensing. Hypertension. 2023;80(8):1580-1589. doi: 10.1161/HYPERTENSIONAHA.123.20577.

34. Stec DE, Juncos LA, Granger JP. Renal intramedullary infusion of tempol normalizes the blood pressure response to intrarenal blockade of heme oxygenase-1 in angiotensin II-dependent hypertension. J Am Soc Hypertens. 2016;10(4):346-351. doi: 10.1016/j.jash.2016.01.023.

35. Kulthinee S, Tasanarong A, Franco M, Navar LG. Interaction of Angiotensin II AT1 Receptors with Purinergic P2X Receptors in Regulating Renal Afferent Arterioles in Angiotensin II-Dependent Hypertension. Int J Mol Sci. 2023;24(14):11413. doi: 10.3390/ijms241411413.

36. Sadri S, Tomar N, Yang C, Audi SH, Cowley AW Jr, Dash RK. Effects of ROS pathway inhibitors and NADH and FADH2 linked substrates on mitochondrial bioenergetics and ROS emission in the heart and kidney cortex and outer medulla. Arch Biochem Biophys. 2023;744:109690. doi: 10.1016/j.abb.2023.109690.

37. Lu X, Crowley SD. Actions of Dendritic Cells in the Kidney during Hypertension. Compr Physiol. 2022;12(3):4087-4101. doi: 10.1002/cphy.c210050.

38. Yang T, Song C, Ralph DL, et al. Cell-Specific Actions of the Prostaglandin E-Prostanoid Receptor 4 Attenuating Hypertension: A Dominant Role for Kidney Epithelial Cells Compared With Macrophages. J Am Heart Assoc. 2022;11(19):e026581. doi: 10.1161/JAHA.122.026581.

39. Sánchez-Lozada LG, Madero M, et al. Sugar, salt, immunity and the cause of primary hypertension. Clin Kidney J. 2023;16(8):1239-1248. doi: 10.1093/ckj/sfad058.

40. Shekhar S, Varghese K, Li M, et al. Conflicting Roles of 20-HETE in Hypertension and Stroke. Int J Mol Sci. 2019;20(18):4500. doi: 10.3390/ijms20184500.

41. Wu X, Zhang N, Yu J, et al. The underlying mechanism of transcription factor IRF1, PRDM1, and ZNF263 involved in the regulation of NPPB rs3753581 on pulse pressure hypertension. Gene. 2023:878:147580. doi: 10.1016/j.gene.2023.147580.

42. Shinohara K, Liu X, Morgan DA, et al. Selective Deletion of the Brain-Specific Isoform of Renin Causes Neurogenic Hypertension. Hypertension. 2016;68(6):1385-1392. doi: 10.1161/HYPERTENSIONAHA.116.08242.

43. Drawz P, Baumann D, Dayton A. Renal denervation: recent developments in clinical and preclinical research. Curr Opin Nephrol Hypertens. 2023;32(5):404-411. doi: 10.1097/MNH.0000000000000908

44. Grassi G, Dell'Oro R, Quarti-Trevano F, et al. Sympathetic Neural Mechanisms in Hypertension: Recent Insights. Curr Hypertens Rep. 2023;25(10):263-270. doi: 10.1007/s11906-023-01254-4.

45. Sonalker PA, Jackson EK. Norepinephrine, via beta-adrenoceptors, regulates bumetanide -sensitive cotransporter type 1 expression in thick ascending limb cells. Hypertension. 2007;49(6):1351-1357.
doi: 10.1161/HYPERTENSIONAHA.107.088732.

46. Richards EM, Li J, Stevens BR, Pepine CJ, Raizada MK. Gut Microbiome and Neuroinflammation in Hypertension. Circ Res. 2022;130(3):401-417. doi: 10.1161/CIRCRESAHA.121.319816.

47. Mahfoud F, Kandzari DE, Kario K, et al. Long-term efficacy and safety of renal denervation in the presence of antihypertensive drugs (SPYRAL HTN-ON MED): a randomised, sham-controlled trial. Lancet. 2022;399(10333): 1401-1410. doi: 10.1016/S0140-6736(22)00455-X.

48. Bhatt DL, Vaduganathan M, Kandzari DE, et al. Long-term outcomes after catheter-based renal artery denervation for resistant hypertension: final follow-up of the randomised SYMPLICITY HTN-3 Trial. Lancet. 2022;400 (10361):1405-1416. doi: 10.1016/S0140-6736(22)01787-1.

49. Osborn JW, Tyshynsky R, Vulchanova L. Function of Renal Nerves in Kidney Physiology and Pathophysiology. Annu Rev Physiol. 202; 83:429-450. doi: 10.1146/annurev-physiol-031620-091656.

50. Wang Z, Zeng C, Villar VA, et al. Human GRK4γ142V variant promotes angiotensin II type I receptor-mediated hypertension via renal histone deacetylase type 1 inhibition. Hypertension. 2016;67(2):325-334. doi: 10.1161/HYPERTENSIONAHA.115.05962.

51. Okuno K, Torimoto K, Cicalese SM, et al. Angiotensin II Type 1A Receptor Expressed in Smooth Muscle Cells is Required for Hypertensive Vascular Remodeling in Mice Infused With Angiotensin II. Hypertension. 2023;80(3):668-677. doi: 10.1161/HYPERTENSIONAHA.122.20601.

52. Kulthinee S, Tasanarong A, Franco M, Navar LG. Interaction of Angiotensin II AT1 Receptors with Purinergic P2X Receptors in Regulating Renal Afferent Arterioles in Angiotensin II-Dependent Hypertension. Int J Mol Sci. 2023;24(14):11413. doi: 10.3390/ijms241411413.

53. Nwia SM, Leite APO, Li XC, Zhuo JL. Sex differences in the renin-angiotensin-aldosterone system and its roles in hypertension, cardiovascular, and kidney diseases. Front Cardiovasc Med. 2023;10:1198090.
doi: 10.3389/fcvm.2023.1198090.

54. Vaz de Castro PAS, Jose PA, Simões E Silva AC. Interactions between the intrarenal dopaminergic and the renin-angiotensin systems in the control of systemic arterial pressure. Clin Sci (Lond). 2022;136(16):1205-1227. doi: 10.1042/CS20220338.

55. Fang YJ, Thomas GN, Xu ZL, Fang J-Q, Critchley JAJH, Tomlinson B. An affected pedigree member analysis of linkage between the dopamine D2 receptor gene TaqI polymorphism and obesity and hypertension. Int J Cardiol. 2005;102(1):111-116. doi: 10.1016/j.ijcard.2004.05.010.

56. Jiang X, Konkalmatt P, Yang Y, et al. Single-nucleotide polymorphisms of the dopamine D2 receptor increase inflammation and fibrosis in human renal proximal tubule cells. Hypertension. 2014;63(3):e74-80. doi: 10.1161/HYPERTENSIONAHA.113.02569.

57. Chrysant SG. The Interaction of Kidneys and Gut in Development of Salt-Sensitive Hypertension. Cardiol Rev. 2023 Jun 5. doi: 10.1097/CRD.0000000000000518.

58. Thomas GN, Critchley JA, Tomlinson B, Cockram CS, Chan JC. Relationships between the taqI polymorphism of the dopamine D2 receptor and blood pressure in hyperglycaemic and normoglycaemic Chinese subjects. Clin Endocrinol (Oxf). 2001;55(5):605-11. doi: 10.1046/j.1365-2265.2001.01404.x.

59. Yang J, Hall JE, Jose PA, et al. Comprehensive insights in GRK4 and hypertension: From mechanisms to potential therapeutics. Pharmacol Ther. 2022;239: 108194. doi: 10.1016/j.pharmthera.2022.108194.

60. Zeng C, Xia T, Zheng S, Liang L, Chen Y. Synergistic Effect of Uroguanylin and D1 Dopamine Receptors on Sodium Excretion in Hypertension. J Am Heart Assoc. 2022;11 (6):e022827. doi: 10.1161/JAHA.121.022827.

61. Banday AA, Lokhandwala MF. Renal Dopamine Oxidation and Inflammation in High Salt Fed Rats. J Am Heart Assoc. 2020;9(1):e014977. doi: 10.1161/JAHA.119.014977.

62. Olivares-Hernández A, Figuero-Pérez L, Cruz-Hernandez JJ, Sarmiento RG, Usagui-Martin R, Miramontes-Gonzales JP. Dopamine Receptors and the Kidney: An Overview of Health- and Pharmacological-Targeted Implications. Biomolecules. 2021;11(2):254. doi: 10.3390/biom11020254.

63. Gildea JJ, Xu P, Kemp BA, Carey RM, Jose PA, Felder RA. The Dopamine D1 Receptor and Angiotensin II Type-2 Receptor are Required for Inhibition of Sodium Transport Through a Protein Phosphatase 2A Pathway. Hypertension. 2019;73(6):1258-1265. doi: 10.1161/HYPERTENSIONAHA.119.12705.

64. Natarajan AR, Eisner GM, Armando I, et al. The Renin-Angiotensin and Renal Dopaminergic Systems Interact in Normotensive Humans. J Am Soc Nephrol. 2016;27(1):265-79. doi: 10.1681/ASN.2014100958. Epub 2015

65. Grossman E, Hoffman A, Tamrat M, Armando I, Keiser HR, Goldstein DS. Endogenous dopa and dopamine responses to dietary salt loading in salt-sensitive rats. J Hypertens. 1991;9(3):259-63.
doi: 10.1097/00004872-199103000-00010.

66. Jiang X, Zhang Y, Yang Y, et al. Gastrin stimulates renal dopamine production by increasing the renal tubular uptake of l-DOPA. Am J Physiol Endocrinol Metab. 2017;312(1): E1-E10.

67. Pinto V, Pinho MJ, Soares-da-Silva P. Renal amino acid transport systems and essential hypertension. FASEB J. 2013;27(8): 2927-38.

68. Hsin Y-H, Tang C-H, Lai H-T, et al. The role of TonEBP in regulation of AAD expression and dopamine production in renal proximal tubule cells upon hypertonic challenge. Biochem Biophys Res Commun. 2011;414(3):598-603.

69. Baines AD, Drangova R, Hatcher C. Dopamine production by isolated glomeruli and tubules from rat kidneys. Can J Physiol Pharmacol. 1985;63(2):155-8.

70. Konkalmatt PR, Asico LD, Zhang Y, et al. Renal rescue of dopamine D2 receptor function reverses renal injury and high blood pressure. JCI Insight. 2016;1(8):e85888.

71. Trivedi M, Lokhandwala MF. Rosiglitazone restores renal D1A receptor-Gs protein coupling by reducing receptor hyperphosphorylation in obese rats. Am J Physiol Renal Physiol. 2005;289(2):F298-304.

72. Miramontes-Gonzalez JP, Hightower CM, Zhang K, et al. A new common functional coding variant at the DDC gene change renal enzyme activity and modify renal dopamine function. Sci Rep. 2019;9(1):5055.

73. Asico LD, Ladines C, Fuchs S, et al. Disruption of the dopamine D3 receptor gene produces renin-dependent hypertension. J Clin Invest.1998;102(3):493-498.

74. Bek MJ, Wang X, Asico LD, et al. Angiotensin-II type 1 receptor-mediated hypertension in D4 dopamine receptor-deficient mice. Hypertension. 2006 Feb;47 (2):288-95.

75. Liu X, Wang W, Chen W, et al. Regulation of blood pressure, oxidative stress and AT1R by high salt diet in mutant human dopamine D5 receptor transgenic mice. Hypertens Res. 2015;38(6):394-9.

76. Hollon TR, Bek MJ, Lachowicz JE, et al. Mice lacking D5 dopamine receptors have increased sympathetic tone and are hypertensive. J Neurosci. 2002;22(24):10801-10.

77. Villar VA, Jones JE, Armando I, et al. G protein-coupled receptor kinase 4 (GRK4) regulates the phosphorylation and function of the dopamine D3 receptor. J Biol Chem. 2009;284(32):21425-1434.

78. Lu X, Ye Z, Zheng S, et al . Long-Term Exposure of Fine Particulate Matter Causes Hypertension by Impaired Renal D1 Receptor-Mediated Sodium Excretion via Upregulation of G-Protein-Coupled Receptor Kinase Type 4 Expression in Sprague-Dawley Rats. J Am Heart Assoc. 2018;7(1):e007185.

79. Wang X, Luo H, Chen C, et al. Prenatal lipopolysaccharide exposure results in dysfunction of the renal dopamine D1 receptor in offspring. Free Radic Biol Med. 2014;76:242-250.

80. Allen SJ, Parthasarathy G, Darke PL, et al. Structure and function of the hypertension variant A486V of G protein-coupled receptor kinase 4. J Biol Chem. 2015;290(33):20360-20373.

81. Padmanabhan S, Caulfield M, Dominiczak AF. Genetic and molecular aspects of hypertension. Circ Res. 2015;116(6):937-959.

82. Sanada H, Yoneda M, Yatabe J, et al. Common variants of the G protein-coupled receptor type 4 are associated with human essential hypertension and predict the blood pressure response to angiotensin receptor blockade. Pharmacogenomics J. 2016;16(1):3-9.

83. Zhang H, Sun ZQ, Liu SS, et al. Association between GRK4 and DRD1 gene polymorphisms and hypertension: a meta-analysis. Clin Interv Aging. 2015;11:17-27.

84. Rayner B, Ramesar R. The importance of G protein-coupled receptor kinase 4 (GRK4) in pathogenesis of salt sensitivity, salt sensitive hypertension and response to antihypertensive treatment. Int J Mol Sci. 2015;16(3):5741-5749.

85. Muskalla AM, Suter PM, Saur M, et al. G-protein receptor kinase 4 polymorphism and response to antihypertensive therapy. Clin Chem. 2014;60(12):1543-1548.

86. Bhatnagar V, O'Connor DT, Brophy VH, et al. G-protein-coupled receptor kinase 4 polymorphisms and blood pressure response to metoprolol among African Americans: sex-specificity and interactions. Am J Hypertens. 2009;22(3):332-8.

87. Vandell AG, Lobmeyer MT, Gawronski BE, et al. G protein receptor kinase 4 polymorphisms: -blocker pharmacogenetics and treatment-related outcomes in hypertension. Hypertension. 2012;60(4):957-64.

88. Lee M, Kim MK, Kim SM, et al. Gender-based differences on the association between salt-sensitive genes and obesity in Korean children aged between 8 and 9 years. PLoS One. 2015;10(3):e0120111.

89. Kimura L, Angeli CB, Auricchio MT, et al. Multilocus family-based association analysis of seven candidate polymorphisms with essential hypertension in an African-derived semi-isolated Brazilian population. Int J Hypertens. 2012;2012:859219.

90. Liu C, Xi B. Pooled analyses of the associations of polymorphisms in the GRK4 and EMILIN1 genes with hypertension risk. Int J Med Sci. 2012;9(4):274-9.

91. Watanabe H, Xu J, Bengra C, et al. Desensitization of human renal D1 dopamine receptors by G protein-coupled receptor kinase 4. Kidney Int. 2002;62(3):790-8.

92. Jiang W, Wang X, Li R, et a; Targeted capture sequencing identifies genetic variations of GRK4 and RDH8 in Han Chinese with essential hypertension in Xinjiang. PLoS One. 2021;16(7):e0255311.

93. Cohn HI, Xi Y, Pesant S, et al. G protein-coupled receptor kinase 2 expression and activity are associated with blood pressure in black Americans. Hypertension. 2009;54(1): 71-76.

94. Tutunea-Fatan E, Caetano FA, Gros R, et al. GRK2 targeted knock-down results in spontaneous hypertension and altered vascular GPCR signaling. J Biol Chem. 2015; 290(8):5141-5155.

95. Gros R, Benovic JL, Tan CM, et al. G-protein-coupled receptor kinase activity is increased in hypertension. J Clin Invest. 1997;99(9):2087-2093.

96. Banday AA, Fazili FR, Lokhandwala MF. Insulin causes renal dopamine D1 receptor desensitization via GRK2-mediated receptor phosphorylation involving phosphatidylinositol 3-kinase and protein kinase C. Am J Physiol Renal Physiol. 2007; 293(3):F877-884.

97. Daigle TL, Ferris MJ, Gainetdinov RR, et al. Selective deletion of GRK2 alters psychostimulant-induced behaviors and dopamine neurotransmission. Neuropsychopharmacology. 2014;39(10):2450-2462.

98. Ito K, Haga T, Lameh J, et al. Sequestration of dopamine D2 receptors depends on coexpression of G-protein-coupled receptor kinases 2 or 5. Eur J Biochem. 1999;260(1): 112-9.

99. Iwata K, Ito K, Fukuzaki A, et al. Dynamin and Rab5 regulate GRK2-dependent internalization of dopamine D2 receptors. Eur J Biochem. 1999;263(2):596-602.

100. Namkung Y, Dipace C, Javitch JA, Sibley DR. G protein-coupled receptor kinase-mediated phosphorylation regulates post-endocytic trafficking of the D2 dopamine receptor. J Biol Chem. 2009;284(22):15038-15051. doi: 10.1074/jbc.M900388200.

101. Crawford CA, Teran A, Ramirez GI, et al. Age-dependent effects of dopamine receptor inactivation on cocaine-induced behaviors in male rats: evidence of dorsal striatal D2 receptor supersensitivity. J Neurosci Res. 2019;97 (12):1546-1558. doi: 10.1002/jnr.24491.

102. Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/ AGS/ APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: executive summary: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. Hypertension. 2018;71(6):1269-1324. doi: 10.1161/HYP.0000000000000066.

103. Burnier M, Monod M, Chiolero A, Maillard M, Nussberger J, Brunner HR. Renal sodium handling in acute and chronic salt loading/depletion protocols: the confounding influence of acute water loading. J Hypertens. 2000;18(11):1657-1664. doi: 10.1097/00004872-200018110-00018.

104. Harrison DG, Coffman TM, Wilcox CS. Pathophysiology of Hypertension: The Mosaic Theory and Beyond. Circ Res. 2021;128(7):847 -863. doi: 10.1161/CIRCRESAHA.121.318082.

105. Dimsdale JE, Ziegler M, Mills P, Berry C. Prediction of salt sensitivity. Am J Hypertens. 1990;3(6 Pt 1):429-35.

106. Castiglioni P, Parati G, Lazzeroni D, et al. Hemodynamic and autonomic response to different salt intakes in normotensive individuals. J Am Heart Assoc. 2016;5(8):e003736. doi: 10.1161/JAHA.116.003736.

107. Overlack A, Ruppert M, Kolloch R, et al. Divergent hemodynamic and hormonal responses to varying salt intake in normotensive subjects. Hypertension. 1993;22 (3):331-338. doi: 10.1161/01.hyp.22.3.331.

108. MacFadyen RJ, Lees KR, Reid JL. Responses to low dose intravenous perindoprilat infusion in salt deplete/salt replete normotensive volunteers. Br J Clin Pharmacol. 1994;38(4): 329-334.
doi: 10.1111/j.1365-2125.1994.tb04362.x.

109. Overlack A, Ruppert M, Kolloch R, Kraft K, Stumpe KO. Age is a major determinant of the divergent blood pressure responses to varying salt intake in essential hypertension. Am J Hypertens. 1995;8(8):829-836. doi: 10.1016/0895-7061(95)00213-9.

110. Longworth DL, Drayer JI, Weber MA, et al. Divergent blood pressure responses during short-term sodium restriction in hypertension. Clin Pharmacol Ther. 1980;27(4):544-6.

111. Mente A, O’Donnell MJ, Rangarajan S, et al. Association of urinary sodium and potassium excretion with blood pressure. N Engl J Med. 2014;371:601-611. doi: 10.1056/NEJMoa1311989.

112. Montasser ME, Douglas JA, Roy-Gagnon M-H, et al. Determinants of Blood Pressure Response to Low Salt Intake in a Healthy Adult Population. J Clin Hypertens (Greenwich). 2011;13(11):795–800. doi: 10.1111/j.1751-7176.2011.00523.x

113. Yoon C-Y, Noh J, Lee J, et al. High and low sodium intakes are associated with incident chronic kidney disease in patients with normal renal function and hypertension. Kidney Int. 2018;93(4):921-931.
doi: 10.1016/j.kint.2017.09.016.

114. Gildea JJ, Xu P, Schiermeyer KA, et al. Inverse Salt Sensitivity of Blood Pressure Is Associated with an Increased Renin-Angiotensin System Activity. Biomedicines. 2022;10(11):0. doi: 10.3390/biomedicines10112811.

115. Xu P, Sudarikova AV, Ilatovskaya DV, et al. Epithelial Sodium Channel Alpha Subunit (αENaC) Is Associated with Inverse Salt Sensitivity of Blood Pressure. Biomedicines. 2022;10(5):981.
doi: 10.3390/biomedicines10050981.

116. Lamelas PM, Mente A, Diaz R, et al. Association of Urinary Sodium Excretion With Blood Pressure and Cardiovascular Clinical Events in 17,033 Latin Americans. Am J Hypertens. 2016;29(7):796-805.
doi: 10.1093/ajh/hpv195.

117. Miller JZ, Weinberger MH, Daugherty SA, Fineberg NS, Christian JC, Grim CE. Heterogeneity of blood pressure response to dietary sodium restriction in normotensive adult. J Chronic Dis. 1987;40(3):245-250. doi: 10.1016/0021-9681(87)90160-3.

118. Alderman MH, Lamport B. Moderate sodium restriction. Do the benefits justify the hazards? Am J Hypertens. 1990;3(6 Pt 1):499-504. doi: 10.1093/ajh/3.6.499.

119. Romberger NT, Stock JM, Patik JC, et al. Inverse salt sensitivity in normotensive adults: role of demographic factors. J Hypertens. 2023;41(6):934-940.

120. He J, Huang J-F, Li C, et al. Sodium sensitivity, sodium resistance, and incidence of hypertension: a longitudinal follow-up study of dietary sodium intervention. Hypertension 2021;78(1):155-164.
doi: 10.1161/HYPERTENSIONAHA.120.16758.

121. Cuka E, Simoni M, Lanzani C, et al. Inverse salt sensitivity: an independent risk factor for cardiovascular damage in essential hypertension. J Hypertens. 2022;40(8):1504-1512. doi: 10.1097/HJH.0000000000003174.

122. Burnier M, Monod M, Chiolero A, et al. Renal sodium handling in acute and chronic salt loading/depletion protocols: the confounding influence of acute water loading. J Hypertens. 2000;18(11):1657-1664. doi: 10.1097/00004872-200018110-00018

123. O’Donnell MJ, Yusuf S, Mente A, et al. Urinary sodium and potassium excretion and risk of cardiovascular events. JAMA. 2011; 306(20):2229-2238. doi: 10.1001/jama.2011.1729.

124. Braam B, Huang X, Cupples WA, Hamza SM. Understanding the two faces of low-salt intake. Curr Hypertens Rep. 2017;19(6):49. doi: 10.1007/s11906-017-0744-z.

125. O'Donnell M, Mente A, Rangarajan S, et al. Joint association of urinary sodium and potassium excretion with cardiovascular events and mortality: prospective cohort study. BMJ. 2019;364:l772.
doi: 10.1136/bmj.l772.

126. O'Donnell M, Mente A, Rangarajan S, et al. Urinary sodium and potassium excretion, mortality, and cardiovascular events. N Engl J Med. 2014;371(7):612-23. doi: 10.1056/NEJMoa1311889.

127. Graudal N, Jurgens G, Baslund G, Alderman MH. Compared With Usual Sodium Intake, Low- and Excessive Sodium Diets Are Associated With Increased Mortality: A Meta-Analysis. Am J Hypertens. 2014;27(9):1129-1137. doi: 10.1093/ajh/hpu028.

128. Hessels NR, Zhu Y, Bakker SJL, de Borst MH, Navis GJ, Riphagen IJ. Low Sodium Intake, Low Protein Intake, and Excess Mortality in an Older Dutch General Population Cohort: Findings in the Prospective Lifelines-MINUTHE Study. Nutrients. 2023;15(2): 428. doi: 10.3390/nu15020428.

129. Stolarz-Skrzypek K, Kuznetsova T, Thijs L, et al. Fatal and nonfatal outcomes, incidence of hypertension, and blood pressure changes in relation to urinary sodium excretion. JAMA. 2011;305(17):1777-1785.
doi: 10.1001/jama.2011.574

130. Thomas MC, Moran J, Forsblom C, et al. The association between dietary sodium intake, ESRD, and all-cause mortality in patients with type 1 diabetes. Diabetes Care. 2011;34(4) :861-866. doi: 10.2337/dc10-1722.

131. Mente A, O’Donnell M, Yusuf S. Sodium Intake and Health: What Should We Recommend Based on the Current Evidence? Nutrients. 2021;13(9):3232. doi: 10.3390/nu13093232.

132. Wang J, Deng Y, Zou X, et al. Long-term low salt diet increases blood pressure by activation of the renin-angiotensin and sympathetic nervous systems. Clin Exp Hypertens. 2019;41(8):739-746.
doi: 10.1080/10641963.2018.1545850

133. Ott CE, Welch WJ, Lorenz JN, Whitescarver SA, Kotchen TA. Effect of salt deprivation on blood pressure in rats. Am J Physiol. 1989;256(5 Pt 2):H1426-1431. doi: 10.1152/ajpheart.1989.256.5.H1426

134. Webb DJ, Clark SA, Brown WB, et al. Dietary sodium deprivation raises blood pressure in the rat but does not produce irreversible hyperaldosteronism. J Hypertens. 1987;5(5):525-531. doi: 10.1097/00004872-198710000-00003.

135. Vari RC, Freeman RH, Davis JO, Sweet WD. Role of renal nerves in rats with low-sodium, one-kidney hypertension. Am J Physiol. 1986;250(2 Pt 2):H189-194. doi: 10.1152/ajpheart.1986.250.2.H189

136. Seymor AA, Davis JO, Freeman RH, et al. Hypertension produced by sodium depletion and unilateral nephrectomy: a new experimental model. Hypertension. 1980;2(2): 125-129. doi: 10.1161/01.hyp.2.2.125.

137. Cook NR, Appel LJ, Whelton PK. Sodium Intake and All-Cause Mortality Over 20 Years in the Trials of Hypertension Prevention. J Am Coll Cardiol. 2016;68(15): 1609-1617. doi: 10.1016/j.jacc.2016.07.745

138. Cappuccio FP, Beer M, Strazzullo P; European Salt Action Network. Population dietary salt reduction and the risk of cardiovascular disease. A scientific statement from the European Salt Action Network. Nutr Metab Cardiovasc Dis. 2018;29(2):107-114. doi: 10.1016/j.numecd.2018.11.010.

139. Cappuccio FP. Campbell NRC, He FJ, et al. Sodium and Health: Old Myths and a Controversy Based on Denial. Curr Nutr Rep. 2022;11(2):172-184. doi: 10.1007/s13668-021-00383-z.

140. Oparil S. Low sodium intake - cardiovascular health benefit or risk? N Engl J Med. 2014;371(7):677-679.
doi: 10.1056/NEJMe1407695.

141. Lindgren N, Usiello A, Goiny M, et al. Distinct roles of dopamine D2L and D2S receptor isoforms in the regulation of protein phosphorylation at presynaptic and postsynaptic sites. Proc Natl Acad Sci USA. 2003;100(7):4305-4309. doi: 10.1073/pnas.0730708100.

142. Li L, Cheng L, Wang Y. Differential roles of two isoforms of dopamine D2 receptors in l-dopa-induced abnormal involuntary movements in mice. Neuroreport. 2021;32 (7):555-561.
doi: 10.1097/WNR.0000000000001623

143. Cokkan KB, Mavri M. Rutland CS, et al. Critical Impact of Different Conserved Endoplasmic Retention Motifs and Dopamine Receptor Interacting Proteins (DRIPs) on Intracellular Localization and Trafficking of the D2 Dopamine Receptor (D2-R) Isoforms. Biomolecules. 2020;10(10):1355. doi: 10.3390/biom10101355.

144. Fontaine R, Affaticati P, Yamamoto K, et al. Dopamine inhibits reproduction in female zebrafish (Danio rerio) via three pituitary D2 receptor subtypes. Endocrinology. 2013;154 (2):807-818. doi: 10.1210/en.2012-1759.

145. Gao DQ, Canessa LM, Mouradian MM, Jose PA. Expression of the D2 subfamily of dopamine receptor genes in kidney. Am J Physiol. 1994;266(4 Pt 2):F646-50. doi: 10.1152/ajprenal.1994.266.4.F646.

146. Rosmond R, Rankinen T, Chagnon M, et al. Polymorphism in exon 6 of the dopamine D(2) receptor gene (DRD2) is associated with elevated blood pressure and personality disorders in men. J Hum Hypertens. 2001; 15(8):553-558. doi: 10.1038/sj.jhh.1001231.

147. Bhatnagar P, Barron-Casella E, Bean CJ, et al. Genome-wide meta-analysis of systolic blood pressure in children with sickle cell disease. PLoS One. 2013;8(9):e74193. doi: 10.1371/journal.pone.0074193.

148. Thomas GN, Tomlinson B, Critchley JA. Modulation of blood pressure and obesity with the dopamine D2 receptor gene TaqI polymorphism. Hypertension. 2000;36(2): 177-182. doi: 10.1161/01.hyp.36.2.177

149. Zhang Y, Cuevas S, Asico LD, et al. Deficient dopamine D2 receptor function causes renal inflammation independently of high blood pressure. PLoS One. 2012;7(6): e38745

150. Asico L, Zhang X, Jiang J, et al. Lack of renal dopamine D5 receptors promotes hypertension. J Am Soc Nephrol. 2011;22(1): 82-89. doi: 10.1681/ASN.2010050533.

151. Armando I, Asico LD, Wang X, et al. Antihypertensive effect of etamicastat in dopamine D2 receptor-deficient mice. Hypertens Res. 2018;41(7):489-498. doi: 10.1038/s41440-018-0041-5.

152. Ozono R, Ueda A, Oishi Y, et al. Dopamine D2 receptor modulates sodium handling via local production of dopamine in the kidney. J Cardiovasc Pharmacol. 2003;42 Suppl 1:S75-79. doi: 10.1097/00005344-200312001-00017.

153. Ueda A, Ozono R, Oshima T, et al. Disruption of the type 2 dopamine receptor gene causes a sodium-dependent increase in blood pressure in mice. Am J Hypertens 2003;16(10):853-858. doi: 10.1016/s0895-7061(03)01013-6.

154. Armando I, Wang X, Villar VA, et al. Reactive oxygen species-dependent hypertension in dopamine D2 receptor-deficient mice. Hypertension. 2007;49(3):672-678. doi: 10.1161/01.HYP.0000254486.00883.3d.

155. Zhang Y, Cuevas S, Asico LD, et al. Deficient dopamine D2 receptor function causes renal inflammation independently of high blood pressure. PLoS One. 2012;7(6): e38745. doi: 10.1371/journal.pone.0038745

156. Schlesinger K, Harkins J, Deckard BS, Paden C. Catechol-O-methyl transferase and monoamine oxidase activities in brains of mice susceptible and resistant to audiogenic seizures. J Neurobiol. 1975;6(6):587-96. doi: 10.1002/neu.480060605.

157. Eleftheriou BE. Regional brain catechol-O-methyl transferase: age related differences in the mouse. Exp Aging Res. 1975;1(1):99-103. doi: 10.1080/03610737508257951.

158. Kumagi A, Takeda S, Sohara E, et al. Dietary Magnesium Insufficiency Induces Salt-Sensitive Hypertension in Mice Associated With Reduced Kidney Catechol-O-Methyl Transferase Activity . Hypertension. 2021;78 (1):138-150. doi: 10.1161/HYPERTENSIONAHA.120.16377.

159. Escano CS, Armando I, Wang X, et al. Renal dopaminergic defect in C57Bl/6J mice. Am J Physiol Regul Integr Comp Physiol. 2009;297(6):R1660-1669. doi: 10.1152/ajpregu.00147.2009.

160. Combe R, Mudgett J, El Fertak L, et al. How does circadian rhythm impact salt sensitivity of blood pressure in mice? A study in two close C57Bl/6 substrains. PLoS One. 2016;11(4):e0153472.
doi: 10.1371/journal.pone.0153472

161. Athirakul K, Kim HS, Audoly LP, Smithies O, Coffman TM. Deficiency of COX-1 causes natriuresis and enhanced sensitivity to ACE inhibition. Kidney Int. 2001;60(6):2324-9. doi: 10.1046/j.1523-1755.2001.00072.x

162. Kopkan L, Hess A, Husková Z, Cervenka L, Navar LG, Majid DS. High-salt intake enhances superoxide activity in eNOS knockout mice leading to the development of salt sensitivity. Am J Physiol Renal Physiol. 2010;299(3):F656-F663. doi: 10.1152/ajprenal.00047.2010.

163. Mangrum AJ, Gomez RA, Norwood VF. Effects of AT(1A) receptor deletion on blood pressure and sodium excretion during altered dietary salt intake. Am J Physiol Renal Physiol. 2002;283(3):F447–F453.
doi: 10.1152/ajprenal.00259.2001.10.

164. Hartner A, Cordasic N, Klanke B, et al. Strain differences in the development of hypertension and glomerular lesions induced by deoxycorticosterone acetate salt in mice. Nephrol Dial Transplant. 2003;18(10):1999-2004. doi: 10.1093/ndt/gfg299.

165. Luft FC, Miller JZ, Grim CE, et al. Salt sensitivity and resistance of blood pressure. Age and race as factors in physiological responses. Hypertension. 1991;17(1 Suppl): I102-8. doi: 10.1161/01.hyp.17.1_suppl.i102.

166. Moore SC, Campisi R, Asico LD, Kumar M, Jose PA, Armando I. The renal mechanisms involved in the response to salt intake are sex related in mice. Hypertension 2023;80:AP383 /doi.org/10.1161/hyp.80.suppl_1.P383

167. Asico LD, Moore S, Jose PA, Armando I. Deletion of the dopamine D2 receptor in the renal proximal tubule increases blood pressure on low salt diet and decreases blood pressure on high salt diet, a case of inverse salt sensitivity. 2021 Kidney Week (Moderated Poster session). PO1814.

168. Gildea JJ, Xu P, Schiermeyer K, Yue W, Carey RM, Jose PA, Felder RA. The etiology of inverse salt sensitivity of blood pressure: miRNA-485-5p binds to the dopamine type 2 receptor (D2R) snp rs6276 and decreases D2R expression. Hypertension 2020;76(Suppl 1): A12. 10.1161/hyp.76.suppl_1.12 (oral presentation).

169. Felder RA, Gildea JJ, Xu P, Yue W, Armando I, Carey RM, Jose PA. Inverse Salt Sensitivity of Blood Pressure: Mechanisms and Potential Relevance for Prevention of Cardiovascular Disease. Curr Hypertens Rep 24(9):361-374, 2022. doi: 10.1007/s11906-022-01201-9.

170. Gildea JJ, Xu P, Schiermeyer KA, et al Inverse Salt Sensitivity of Blood Pressure Is Associated with an Increased Renin-Angiotensin System Activity. Biomedicines. 2022;10(11):0.
doi: 10.3390/biomedicines10112811.

171. Xu P, Sudarikova AV, Ilatovskaya DV et al. Epithelial Sodium Channel Alpha Subunit (αENaC) Is Associated with Inverse Salt Sensitivity of Blood Pressure. Biomedicines. 2022;10(5):981.
doi: 10.3390/biomedicines10050981.

172. Li H, Shi S, Sun YH, et al. Dopamine D2 receptor stimulation inhibits angiotensin II-induced hypertrophy in cultured neonatal rat ventricular myocytes. Clin Exp Pharmacol Physiol. 2009;36(3):312-318.
doi: 10.1111/j.1440-1681.2008.05064.x.

173. Durdagi S, Erol I, Salmas RE, et al. Oligomerization and cooperativity in GPCRs from the perspective of the angiotensin AT1 and dopamine D2 receptors. Neurosci Lett. 2019;700:30-37. doi: 10.1016/j.neulet.2018.04.028

174. Wang X, Li F, Jose PA, et al. Reduction of renal dopamine receptor expression in obese Zucker rats: role of sex and angiotensin II. Am J Physiol Renal Physiol. 2010;299(5): F1164-1170. doi: 10.1152/ajprenal.00604.2009.

175. Hussain T, Abdul-Wahab R, Kotak DK, et al. Bromocriptine regulates angiotensin II response on sodium pump in proximal tubules. Hypertension. 1998;32(6):1054-1059. doi: 10.1161/01.hyp.32.6.1054.

176. Zhang MZ, Yao B, Fang X, et al. Intrarenal dopaminergic system regulates renin expression. Hypertension. 2009;53(3): 564-570. doi:10.1161/HYPERTENSIONAHA.108.127035

177. Yang S, Yao B, Zhou Y, et al. Intrarenal dopamine modulates progressive angiotensin II-mediated renal injury. Am J Physiol Renal Physiol. 2012;302(6):F742-9.
doi: 10.1152/ajprenal.00583.2011.

178. Matsuyama T, Ohashi N, Ishigaki S, et al. The relationship between the intrarenal dopamine system and intrarenal renin-angiotensin system depending on the renal function. Intern Med. 2018;57(22):3241-3247. doi: 10.2169/internalmedicine.0994-18.

179. Drake CR Jr, Ragsdale NV, Kaiser DL, et al. Dopaminergic suppression of angiotensin II-induced aldosterone secretion in man: differential responses during sodium loading and depletion. Metabolism. 1984;33(8):696-702. doi: 10.1016/0026-0495(84)90207-5.

180. Barnett R, Singhal PC, Scharschmidt LA, et al. Dopamine attenuates the contractile response to angiotensin II in isolated rat glomeruli and cultured mesangial cells. Circ Res 1986;59(5):529-533.
doi: 10.1161/01.res.59.5.529

181. Kouyoumdzian NM, Rukavina Mikusic NL, et al. Acute infusion of angiotensin II regulates organic cation transporters function in the kidney: its impact on the renal dopaminergic system and sodium excretion. Hypertens Res. 2021;44(3):286-298. doi: 10.1038/s41440-020-00552-7.

182. Rukavina Mikusic NL, Kouyoumdzian NM, et al. Losartan prevents the imbalance between renal dopaminergic and renin angiotensin systems induced by fructose overload. l-Dopa/dopamine index as new potential biomarker of renal dysfunction. Metabolism. 2018;85:271-285. doi: 10.1016/j.metabol.2018.04.010.

183. Yamaguchi I, Yao L, Sanada H, et al. Dopamine D1A receptors and renin release in rat juxtaglomerular cells. Hypertension. 1997;29(4):962-8. doi: 10.1161/01.hyp.29.4.962.

184. Zeng C, Asico LD, Wang X, et al. Angiotensin II regulation of AT1 and D3 dopamine receptors in renal proximal tubule cells of SHR. Hypertension. 2003;41(3 Pt 2):724-9. doi: 10.1161/01.HYP.0000047880.78462.0E..

185. Gross M-L P. Koch A, Mühlbauer B, et al. Renoprotective effect of a dopamine D3 receptor antagonist in experimental type II diabetes. Lab Invest. 2006;86(3):262-74. doi: 10.1038/labinvest.3700383.

186. Sanada H, Yao L, Jose PA, et al. Dopamine D3 receptors in rat juxtaglomerular cells. Clin Exp Hypertens. 1997;19(1-2):93-105. doi: 10.3109/10641969709080807.

187. Luippold G, Max A, Albinus M, et al. Role of the renin-angiotensin system in the compensation of quinpirole-induced blood pressure decrease. Naunyn Schmiedebergs Arch Pharmacol. 200;367(5):427-33. doi: 10.1007/s00210-003-0740-5.

188. Chen K, Deng K, Wang X, et al. Activation of D4 Dopamine Receptor Decreases Angiotensin II Type 1 Receptor Expression in Rat Renal Proximal Tubule Cells. Hypertension. 2015;65(1):153-60.
doi: 10.1161/HYPERTENSIONAHA.114.04038.

189. Moore SC, Vaz de Castro PAS, Yaqub D, et al. Anti-Inflammatory Effects of Peripheral Dopamine. Int J Mol Sci. 2023;24(18):13816. doi: 10.3390/ijms241813816.

190. Rukavina Mikusic NL, Silva MG, Mazzitelli LR, et al. Interaction Between the Angiotensin-(1-7) Mas Receptor and the Dopamine D2 Receptor: Implications in Inflammation. Hypertension and Inflammation – Hypertension. 2021;77(5):1659-1669. doi: 10.1161/HYPERTENSIONAHA.120.16614.

191. Feng Y, Lu Y. Immunomodulatory Effects of Dopamine in Inflammatory Diseases. Front Immunol. 2021:12:663102. doi: 10.3389/fimmu.2021.663102.

192. Yang J, Villar VAM, Jose PA, et al. Renal Dopamine Receptors and Oxidative Stress: Role in Hypertension. Antioxid Redox Signal. 2021;34(9):716-735. doi: 10.1089/ars.2020.8106.

193. Banday AA, Lau YS, Lokhandwala MF. Oxidative stress causes renal dopamine D1 receptor dysfunction and salt-sensitive hypertension in Sprague-Dawley rats. Hypertension. 2008;51(2):367-75.
doi: 10.1161/HYPERTENSIONAHA.107.102111.

194. Xia XG, Schmidt N, Teismann P, et al. Dopamine mediates striatal malonate toxicity via dopamine transporter-dependent generation of reactive oxygen species and D2 but not D1 receptor activation. J Neurochem. 2001;79 (1):63-70. doi: 10.1046/j.1471-4159.2001.00525.x.

195. Charvin D, Vanhoutte P, Pagès C, et al. Unraveling a role for dopamine in Huntington's disease: the dual role of reactive oxygen species and D2 receptor stimulation. Proc Natl Acad Sci USA. 2005;102(34):12218-12223. doi: 10.1073/pnas.0502698102.

196. Cosentino M, Rasini R, Colombo C, et al. Dopaminergic modulation of oxidative stress and apoptosis in human peripheral blood lymphocytes: evidence for a D1-like receptor-dependent protective effect. Free Radic Biol Med. 2004;36(10):1233-40. doi: 10.1016/j.freeradbiomed.2004.02.065.

197. Acquier AB, Mori Sequeiros García M, Gorostizaga AB, et al. Reactive oxygen species mediate dopamine-induced signaling in renal proximal tubule cells. FEBS Lett. 2013;587(19):3254-60.
doi: 10.1016/j.febslet.2013.08.020.

198. Rosin C, Colombo S, Calver AA, et al. Dopamine D2 and D3 receptor agonists limit oligodendrocyte injury caused by glutamate oxidative stress and oxygen/glucose deprivation. Glia. 2005;52(4):336-43.
doi: 10.1002/glia.20250.

199. Odaka H, Numakawa T, Adachi N, et al. Cabergoline, dopamine D2 receptor agonist, prevents neuronal cell death under oxidative stress via reducing excitotoxicity. PLoS One. 2014;9(6):e99271.
doi: 10.1371/journal.pone.0099271.

200. Oster S, Radad K, Scheller D, et al. Rotigotine protects against glutamate toxicity in primary dopaminergic cell culture. Eur J Pharmacol. 2014:724:31-42. doi: 10.1016/j.ejphar.2013.12.014.

201. Niewiarowska-Sendo A, Kozik A, Guevara-Lora I. Influence of bradykinin B2 receptor and dopamine D2 receptor on the oxidative stress, inflammatory response, and apoptotic process in human endothelial cells. PLoS One. 2018 Nov 14;13(11):e0206443. doi: 10.1371/journal.pone.0206443.

202. Cuevas S, Yang Y, Konkalmatt P, et al. Role of nuclear factor erythroid 2-related factor 2 in the oxidative stress-dependent hypertension associated with the depletion of DJ-1. Hypertension. 2015;65(6):1251-1257. doi: 10.1161/HYPERTENSIONAHA.114.0452

203. Lieberknecht V, Junqueira SC, Cunha MP. et al. Pramipexole, a Dopamine D2/D3 Receptor-Preferring Agonist, Prevents Experimental Autoimmune Encephalomyelitis Development in Mice. Mol Neurobiol. 2017;54(2):1033-1045. doi: 10.1007/s12035-016-9717-5.

204. Shibagaki K, Okamoto K, Katsuta O, Nakamura M. Beneficial protective effect of pramipexole on light-induced retinal damage in mice. Exp Eye Res. 2015:139:64-72. doi: 10.1016/j.exer.2015.07.007.

205. Wang Z, Guan W, Han Y, et al. Stimulation of Dopamine D3 Receptor Attenuates Renal Ischemia-Reperfusion Injury via Increased Linkage With Gα12. Transplantation. 2015;99 (11):2274-84.
doi: 10.1097/TP.0000000000000762.

206. Ferrari-Toninelli G, Maccarinelli G, Uberti D, Buerger E, Memo M. Mitochondria-targeted antioxidant effects of S(-) and R(+) pramipexole. BMC Pharmacol. 2010:10:2. doi: 10.1186/1471-2210-10-2.

207. Liu X, Guo Y, Yang Y, et al. DRD4 (DopamineD4Receptor) Mitigate Abdominal Aortic Aneurysm via Decreasing P38 MAPK (mitogen-activated protein kinase)/NOX4 (NADPH Oxidase 4) Axis-Associated Oxidative Stress. Hypertension. 2021;78(2):294-307. doi: 10.1161/HYPERTENSIONAHA.120.16738.

208. Shimada S, Hirabayashi M, Ishige K, et al. Activation of dopamine D4receptors is protective against hypoxia/reoxygenation-induced cell death in HT22 cells. J Pharmacol Sci. 2010;114(2):217-24.
doi: 10.1254/jphs.10134fp.

209. Ishige K, Chen Q, Sagara Y, Schubert D. The activation of dopamine D4 receptors inhibits oxidative stress-induced nerve cell death. J Neurosci. 2001;21(16):6069-76. doi: 10.1523/JNEUROSCI.21-16-06069.2001.

210. Li XX, Bek M, Asico LD, et al. Adrenergic and endothelin B receptor-dependent hypertension in dopamine receptor type-2 knockout mice. Hypertension. 2001;38(3): 303-8. doi: 10.1161/01.hyp.38.3.303.

211. Martinez-Pinilla E, Rodriguez-Perez AI, Navarro G, et al. Dopamine D2 and angiotensin II type 1 receptors form functional heteromers in rat striatum. B Biochem Pharmacol. 2015;96 (2):131-42. doi: 10.1016/j.bcp.2015.05.006.

212. Camargo LL, Wang Y, Rios FJ, McBride M, Montezano AC, Touyz RM. Oxidative Stress and Endoplasmic Reticular Stress Interplay in the Vasculopathy of Hypertension. Can J Cardiol. 2023;39(12):1874-1887. doi: 10.1016/j.cjca.2023.10.012.

213. Qaddumi WN, Jose PA. The Role of the Renal Dopaminergic System and Oxidative Stress in the Pathogenesis of Hypertension. Biomedicines. 2021;9(2):139. doi:10.3390/biomedicines9020139.

214. Didik S, Wang H, James AS, Slotabec L, Li J. Sestrin2 as a Potential Target in Hypertension. Diagnostics (Basel). 2023;13 (14):2374. doi: 10.3390/diagnostics13142374.

215. Cowley AW Jr, Abe M, Mori T, et al. Reactive oxygen species as important determinants of medullary flow, sodium excretion, and hypertension. Am J Physiol Renal Physiol. 2015;308(3):F179-97.
doi: 10.1152/ajprenal.00455.2014.

216. Cuevas S, Zhang Y, Yang Y, et al. Role of renal DJ-1 in the pathogenesis of hypertension associated with increased reactive oxygen species production. Hypertension. 2012;59(2): 446-52.
doi: 10.1161/HYPERTENSIONAHA.111.185744.

217. Yang Y, Zhang Y, Cuevas S., et al. Paraoxonase 2 decreases renal reactive oxygen species production, lowers blood pressure, and mediates dopamine D2 receptor-induced inhibition of NADPH oxidase. Free Radic Biol Med. 2012;53(3):437-446. doi:10.1016/j.freeradbiomed.2012.05.015.

218. Yang Y, Cuevas S, Yang S, et al. Sestrin2 decreases renal oxidative stress, lowers blood pressure, and mediates dopamine D2 receptor- induced inhibition of reactive oxygen species production. Hypertension. 2014;64(4):825-32. doi: 10.1161/HYPERTENSIONAHA.114.03840.

219. Cuevas S, Villar VA, Jose PA, Armando I. Renal dopamine receptors, oxidative stress, and hypertension. Int J Mol Sci. 2013;14(9): 17553-72. doi: 10.3390/ijms140917553.

220. Lassègue B, San Martín A, Griendling KK. Biochemistry, physiology, and pathophysiology of NADPH oxidases in the cardiovascular system. Circ Res. 2012;110(10): 1364-90. doi: 10.1161/CIRCRESAHA.111.243972.

221. Touyz RM, Anagnostopoulou A, Camargo LL, Rios RJ, Montezano AC. Vascular Biology of Superoxide-Generating NADPH Oxidase 5-Implications in Hypertension and Cardiovascular Disease. Antioxid Redox Signal. 2019;30(7):1027-1040. doi: 10.1089/ars.2018.7583.

222. Yu P, Han W, Villar VAM et al. Unique role of NADPH oxidase 5 in oxidative stress in human renal proximal tubule cells. Redox Biol. 2014:2:570-9. doi: 10.1016/j.redox.2014.01.020.

223. Tanase DM, Apostol AG, Costea CF, et al. Oxidative Stress in Arterial Hypertension (HTN): The Nuclear Factor Erythroid Factor 2-Related Factor 2 (Nrf2) Pathway, Implications and Future Perspectives. Pharmaceutics. 2022; 14(3):534. doi: 10.3390/pharmaceutics14030534.

224. Bao B, Liu H, Han Y, Xu L, Xing W, Li Z. Simultaneous Elimination of Reactive Oxygen Species and Activation of Nrf2 by Ultrasmall Nanoparticles to Relieve Acute Kidney Injury. ACS Appl Mater Interfaces. 2023;15(13): 16460-16470. doi: 10.1021/acsami.3c00052.

225. Wan SR, Teng FY, Fan W, et al. BDH1-mediated βOHB metabolism ameliorates diabetic kidney disease by activation of NRF2-mediated antioxidative pathway. Aging (Albany NY). 2023;15(22):13384-13410. doi: 10.18632/aging.205248.

226. Mapuskar KA, Pulliam CF, Zepeda-Orozco D, et al. Redox Regulation of Nrf2 in Cisplatin-Induced Kidney Injury. Antioxidants (Basel). 2023;12(9):1728.
doi: 10.3390/antiox12091728.

227. Wang C, Luo Z, Carter G. NRF2 prevents hypertension, increased ADMA, microvascular oxidative stress, and dysfunction in mice with two weeks of ANG II infusion. Am J Physiol Regul Integr Comp Physiol. 2018;314(3): R399-R406. doi: 10.1152/ajpregu.00122.2017.

228. Goldberg MS, Pisani A, Haburcak M, et al. Nigrostriatal dopaminergic deficits and hypokinesia caused by inactivation of the familial Parkinsonism-linked gene DJ-1. Neuron. 2005;45(4):489-96.
doi: 10.1016/j.neuron.2005.01.041.

229. Yin L, Li H, Liu Z, Wu W, Cai J, Tang C, Dong Z. PARK7 Protects Against Chronic Kidney Injury and Renal Fibrosis by Inducing SOD2 to Reduce Oxidative Stress. Front Immunol. 2021:12:690697.
doi: 10.3389/fimmu.2021.690697.

230. Cuevas S, Yang Y, Konkalmatt P, et al. Role of nuclear factor erythroid 2-related factor 2 in the oxidative stress-dependent hypertension associated with the depletion of DJ-1. Hypertension. 2015;65(6):1251-7. doi: 10.1161/HYPERTENSIONAHA.114.04525.

231. Carey RM, Thorner O, Ortt EM. Dopaminergic inhibition of metoclopramide-induced aldosterone secretion in man. Dissociation of responses to dopamine and bromocriptine. J Clin Invest. 1980;66(1):10-18. doi: 10.1172/JCI109822.

232. Chang H-W, Chu T-S, Huang H-W, et al. Down-regulation of D2 dopamine receptor and increased protein kinase Cmu phosphorylation in aldosterone-producing adenoma play roles in aldosterone overproduction. J Clin Endocrinol Metab. 2007;92(5):1863-70. doi: 10.1210/jc.2006-2338.

233. Miyata K, Rahman M, Shokoji T, et al. Aldosterone stimulates reactive oxygen species production through activation of NADPH oxidase in rat mesangial cells. J Am Soc Nephrol. 2005;16:2906–2912.
doi: 10.1681/ASN.2005040390.

234. Fernandes MH, Soares-da-Silva P. Role of monoamine oxidase and catechol-O-methyltransferase in the metabolism of renal dopamine. J Neural Transm Suppl. 1994:41: 101-5. doi: 10.1007/978-3-7091-9324-2_13.

235. De Marchi U, Mancon M, Battaglia V, Ceccon S, Cardellini P, Toninello A. Influence of reactive oxygen species production by monoamine oxidase activity on aluminum-induced mitochondrial permeability transition. Cell Mol Life Sci. 2004;61(19-20):2664-71. doi: 10.1007/s00018-004-4236-3.

236. Vindis C, Séguélas MH, Lanier S, Parini A, Cambon C. Dopamine induces ERK activation in renal epithelial cells through H2O2 produced by monoamine oxidase. Kidney Int. 2001;59(1):76-86.
doi: 10.1046/j.1523-1755.2001.00468.x.

237. Bianchi P, Séguélas M-H, Parini A, Cambon C. Activation of pro-apoptotic cascade by dopamine in renal epithelial cells is fully dependent on hydrogen peroxide generation by monoamine oxidases. J Am Soc Nephrol. 2003;14(4):855-862. doi: 10.1097/01.asn.0000058909.00567.5c.

238. Seif-El-Nasr M, Atia AS, Abdelsalam RM. Effect of MAO-B inhibition against ischemia-induced oxidative stress in the rat brain. Comparison with a rational antioxidant. Arzneimittelforschung. 2008;58(4):160-7. doi: 10.1055/s-0031-1296487.

239. Zhang XR, Wang YX, Zhang ZJ, Li L, Reynolds GP. The effect of chronic antipsychotic drug on hypothalamic expression of neural nitric oxide synthase and dopamine D2 receptor in the male rat. PLoS One. 2012;7(4): e33247. doi: 10.1371/journal.pone.0033247.

240. Pyne-Geithman GJ, Caudell DN, Cooper M, Clark JF, Shutter LA. Dopamine D2-receptor-mediated increase in vascular and endothelial NOS activity ameliorates cerebral vasospasm after subarachnoid hemorrhage in vitro. Neurocrit Care. 2009;10(2):225-31. doi: 10.1007/s12028-008-9143-2.

241. Wilcox, C.S. Oxidative stress and nitric oxide deficiency in the kidney: A critical link to hypertension? Am J Physiol Regul Integr Comp Physiol. 2005;289(4):R913-35. doi: 10.1152/ajpregu.00250.2005.

242. Duan J, Wainwright MS, Comeron JM, et al. Synonymous mutations in the human dopamine receptor D2 (DRD2) affect mRNA stability and synthesis of the receptor. Hum Mol Genet. 2003;12(3):205-16.
doi: 10.1093/hmg/ddg055.

243. Gholipour N, Ohradanova-Repic A, Ahangari G. A novel report of MiR-4301 induces cell apoptosis by negatively regulating DRD2 expression in human breast cancer cells. J Cell Biochem. 2018;119(8):6408-6417. doi: 10.1002/jcb.26577.

244. Bhatnagar P, Barron-Casella E, Bean CJ, et al. Genome-wide meta-analysis of systolic blood pressure in children with sickle cell disease. PLoS One. 2013;8(9):e74193. doi: 10.1371/journal.pone.007419.

245. Nguweneza A, Oosterwyk C, Banda K, et al. Factors associated with blood pressure variation in sickle cell disease patients: a systematic review and meta-analyses. Expert Rev Hematol. 2022;15(4):359-368. doi: 10.1080/17474086.2022.2043743.

246. Han F, Konkalmatt P, Chen J, et al. miR-217 mediates the protective effects of the dopamine D2 receptor on fibrosis in human renal proximal tubule cells. Hypertension. 2015; 65(5): 1118–1125.
doi:10.1161/HYPERTENSIONAHA.114.05096

247. Xie J, Li S, Ma X, Li R, Zhang H, Li J, Yan X. MiR-217-5p inhibits smog (PM2.5)-induced inflammation and oxidative stress response of mouse lung tissues and macrophages through targeting STAT1. Aging (Albany NY). 2022; 14(16):6796-6808. doi: 10.18632/aging.20425.

248. Zhang H, Chen F, Liang Z, et al. Analysis of miRNAs and their target genes associated with mucosal damage caused by transport stress in the mallard duck intestine. PLoS One. 2020;15(8):e0237699.
doi: 10.1371/journal.pone.0237699.

249. Shi L, Tian Z, Fu Q, Li H, Zhang L, Tian L, Mi W. miR-217-regulated MEF2D-HDAC5/ND6 signaling pathway participates in the oxidative stress and inflammatory response after cerebral ischemia. Brain Res. 2020:1739:146835. doi: 10.1016/j.brainres.2020.14683

250. Yan J, Yang F, Wang D, Lu Y, Liu L, Wang Z. MicroRNA-217 modulates inflammation, oxidative stress, and lung injury in septic mice via SIRT1. Free Radic Res. 2021;55(1):1-10. doi: 10.1080/10715762.2020.1852234.