Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Dopamine D5 receptor-mediated decreases in mitochondrial reactive oxygen species production are cAMP and autophagy dependent

Hypertension Research volume 44, pages 628–641 (2021)Cite this article

Abstract

Overproduction of reactive oxygen species (ROS) plays an important role in the pathogenesis of hypertension. The dopamine D5 receptor (D5R) is known to decrease ROS production, but the mechanism is not completely understood. In HEK293 cells overexpressing D5R, fenoldopam, an agonist of the two D1-like receptors, D1R and D5R, decreased the production of mitochondria-derived ROS (mito-ROS). The fenoldopam-mediated decrease in mito-ROS production was mimicked by Sp-cAMPS but blocked by Rp-cAMPS. In human renal proximal tubule cells with DRD1 gene silencing to eliminate the confounding effect of D1R, fenoldopam still decreased mito-ROS production. By contrast, Sch23390, a D1R and D5R antagonist, increased mito-ROS production in the absence of D1R, D5R is constitutively active. The fenoldopam-mediated inhibition of mito-ROS production may have been related to autophagy because fenoldopam increased the expression of the autophagy hallmark proteins, autophagy protein 5 (ATG5), and the microtubule-associated protein 1 light chain (LC)3-II. In the presence of chloroquine or spautin-1, inhibitors of autophagy, fenoldopam further increased ATG5 and LC3-II expression, indicating an important role of D5R in the positive regulation of autophagy. However, when autophagy was inhibited, fenoldopam was unable to inhibit ROS production. Indeed, the levels of these autophagy hallmark proteins were decreased in the kidney cortices of Drd5−/− mice. Moreover, ROS production was increased in mitochondria isolated from the kidney cortices of Drd5−/− mice, relative to Drd5+/+ littermates. In conclusion, D5R-mediated activation of autophagy plays a role in the D5R-mediated inhibition of mito-ROS production in the kidneys.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Araujo M, Wilcox CS. Oxidative stress in hypertension: role of the kidney. Antioxid Redox Signal. 2014;20:74–101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Loperena R, Harrison DG. Oxidative stress and hypertensive diseases. Med Clin North Am. 2017;101:169–93.

    Article  PubMed  Google Scholar 

  3. Montezano AC, Dulak-Lis M, Tsiropoulou S, Harvey A, Briones AM, Touyz RM. Oxidative stress and human hypertension: vascular mechanisms, biomarkers, and novel therapies. Can J Cardiol. 2015;31:631–41.

    Article  PubMed  Google Scholar 

  4. Addabbo F, Montagnani M, Goligorsky MS. Mitochondria and reactive oxygen species. Hypertension. 2009;53:885–92.

    Article  CAS  PubMed  Google Scholar 

  5. Zhang MZ, Harris RC. Antihypertensive mechanisms of intra-renal dopamine. Curr Opin Nephrol Hypertens. 2015;24:117–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Asghar M, Tayebati SK, Lokhandwala MF, Hussain T. Potential dopamine-1 receptor stimulation in hypertension management. Curr Hypertens Rep. 2011;13:294–302.

    Article  CAS  PubMed  Google Scholar 

  7. Zeng C, Jose PA. Dopamine receptors: important antihypertensive counterbalance against hypertensive factors. Hypertension. 2011;57:11–7.

    Article  CAS  PubMed  Google Scholar 

  8. Allayee H, de Bruin TW, Michelle Dominguez K, Cheng LS, Ipp E, Cantor RM, et al. Genome scan for blood pressure in Dutch dyslipidemic families reveals linkage to a locus on chromosome 4p. Hypertension. 2001;38:773–8.

    Article  CAS  PubMed  Google Scholar 

  9. Cohn DH, Shohat T, Yahav M, Ilan T, Rechavi G, King L, et al. A locus for an autosomal dominant form of progressive renal failure and hypertension at chromosome 1q21. Am J Hum Genet. 2000;67:647–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Yang Z, Asico LD, Yu P, Wang Z, Jones JE, Escano CS, et al. D5 dopamine receptor regulation of reactive oxygen species production, NADPH oxidase, and blood pressure. Am J Physiol Regul Integr Comp Physiol. 2006;290:R96–104.

    Article  CAS  PubMed  Google Scholar 

  11. Saez F, Hong NJ, Garvin JL. Luminal flow induces NADPH oxidase 4 translocation to the nuclei of thick ascending limbs. Physiol Rep. 2016;4:e12724.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Yang Q, Wu FR, Wang JN, Gao L, Jiang L, Li HD, et al. Nox4 in renal diseases: an update. Free Radic Biol Med. 2018;124:466–72.

    Article  CAS  PubMed  Google Scholar 

  13. Haque MZ, Majid DS. Reduced renal responses to nitric oxide synthase inhibition in mice lacking the gene for gp91phox subunit of NAD(P)H oxidase. Am J Physiol Ren Physiol. 2008;295:F758–64.

    Article  CAS  Google Scholar 

  14. Ryter SW, Bhatia D, Choi ME. Autophagy: a lysosome-dependent process with implications in cellular redox homeostasis and human disease. Antioxid Redox Signal. 2019;30:138–59.

    Article  CAS  PubMed  Google Scholar 

  15. Green DR, Levine B. To be or not to be? How selective autophagy and cell death govern cell fate. Cell. 2014;157:65–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Dikic I, Elazar Z. Mechanism and medical implications of mammalian autophagy. Nat Rev Mol Cell Biol. 2018;19:349–64.

    Article  CAS  PubMed  Google Scholar 

  17. Woodall BP, Gustafsson AB. Autophagy—a key pathway for cardiac health and longevity. Acta Physiol. 2018;20:e13074.

    Article  CAS  Google Scholar 

  18. Sanderson RD, Elkin M, Rapraeger AC, Ilan N, Vlodavsky I. Heparanase regulation of cancer, autophagy and inflammation: new mechanisms and targets for therapy. FEBS J. 2017;284:42–55.

    Article  CAS  PubMed  Google Scholar 

  19. Peña-Oyarzun D, Bravo-Sagua R, Diaz-Vega A, Aleman L, Chiong M, Garcia L, et al. Autophagy and oxidative stress in non-communicable diseases: a matter of the inflammatory state. Free Radic Biol Med. 2018;124:61–78.

    Article  PubMed  CAS  Google Scholar 

  20. Wible DJ, Bratton SB. Reciprocity in ROS and autophagic signaling. Curr Opin Toxicol. 2018;7:28–36.

    Article  PubMed  Google Scholar 

  21. Gildea JJ, Wang X, Jose PA, Felder RA. Differential D1 and D5 receptor regulation and degradation of the angiotensin type 1 receptor. Hypertension. 2008;51:360–6.

    Article  CAS  PubMed  Google Scholar 

  22. Jean-Charles PY, Snyder JC, Shenoy SK. Ubiquitination and deubiquitination of G protein-coupled receptors. Prog Mol Biol Transl Sci. 2016;141:1–55.

    Article  CAS  PubMed  Google Scholar 

  23. Li H, Armando I, Yu P, Escano C, Mueller SC, Asico L, et al. Dopamine 5 receptor mediates Ang II type 1 receptor degradation via a ubiquitin-proteasome pathway in mice and human cells. J Clin Investig. 2008;118:2180–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Hollon TR, Bek MJ, Lachowicz JE, Ariano MA, Mezey E, Ramachandran R, et al. Mice lacking D5 dopamine receptors have increased sympathetic tone and are hypertensive. J Neurosci. 2002;22:10801–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Sanada H, Jose PA, Hazen-Martin D, Yu PY, Xu J, Bruns DE, et al. Dopamine-1 receptor coupling defect in renal proximal tubule cells in hypertension. Hypertension. 1999;33:1036–42.

    Article  CAS  PubMed  Google Scholar 

  26. O’Connell DP, Botkin SJ, Ramos SI, Sibley DR, Ariano MA, Felder RA, et al. Localization of dopamine D1A receptor protein in rat kidneys. Am J Physiol. 1995;268:F1185–97.

    PubMed  Google Scholar 

  27. Ennis RC, Asico LD, Armando I, Yang J, Feranil JB, Jurgens JA, et al. Dopamine D1-like receptors regulate the α1A-adrenergic receptor in human renal proximal tubule cells and D1-like dopamine receptor knockout mice. Am J Physiol Ren Physiol. 2014;307:F1238–48.

    Article  CAS  Google Scholar 

  28. Wang X, Li F, Jose PA, Ecelbarger CM. Reduction of renal dopamine receptor expression in obese Zucker rats: role of sex and angiotensin II. Am J Physiol Ren Physiol. 2010;299:F1164–70.

    Article  CAS  Google Scholar 

  29. Li H, Li HF, Felder RA, Periasamy A, Jose PA. Actin cytoskeleton-dependent Rab GTPase-regulated angiotensin type I receptor lysosomal degradation studied by fluorescence lifetime imaging microscopy. J Biomed Opt. 2008;13:031206.

    Article  PubMed  CAS  Google Scholar 

  30. Lee H, Abe Y, Lee I, Shrivastav S, Crusan AP, Huttemann M, et al. Increased mitochondrial activity in renal proximal tubule cells from young spontaneously hypertensive rats. Kidney Int. 2014;85:561–9.

    Article  CAS  PubMed  Google Scholar 

  31. Lee I, Salomon AR, Ficarro S, Mathes I, Lottspeich F, Grossman LI, et al. cAMP-dependent tyrosine phosphorylation of subunit I inhibits cytochrome c oxidase activity. J Biol Chem. 2005;280:6094–100.

    Article  CAS  PubMed  Google Scholar 

  32. Polster BM, Nicholls DG, Ge SX, Roelofs BA. Use of potentiometric fluorophores in the measurement of mitochondrial reactive oxygen species. Methods Enzymol. 2014;547:225–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Votyakova TV, Reynolds IJ. Detection of hydrogen peroxide with Amplex Red: interference by NADH and reduced glutathione auto-oxidation. Arch Biochem Biophys. 2004;431:138–44.

    Article  CAS  PubMed  Google Scholar 

  34. Lochner A, Moolman JA. The many faces of H89: a review. Cardiovasc Drug Rev. 2006;24:261–74.

    Article  CAS  PubMed  Google Scholar 

  35. Gimenez-Xavier P, Francisco R, Santidrian AF, Gil J, Ambrosio S. Effects of dopamine on LC3-II activation as a marker of autophagy in a neuroblastoma cell model. Neurotoxicology. 2009;30:658–65.

    Article  CAS  PubMed  Google Scholar 

  36. Mauthe M, Orhon I, Rocchi C, Zhou X, Luhr M, Hijlkema KJ, et al. Chloroquine inhibits autophagic flux by decreasing autophagosome-lysosome fusion. Autophagy. 2018;14:1435–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Kirkman DL, Muth BJ, Ramick MG, Townsend RR, Edwards DG. Role of mitochondria-derived reactive oxygen species in microvascular dysfunction in chronic kidney disease. Am J Physiol Ren Physiol. 2018;314:F423–9.

    Article  CAS  Google Scholar 

  38. Bonora M, Wieckowski MR, Sinclair DA, Kroemer G, Pinton P, Galluzzi L. Targeting mitochondria for cardiovascular disorders: therapeutic potential and obstacles. Nat Rev Cardiol. 2019;16:33–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Griendling KK, Touyz RM, Zweier JL, Dikalov S, Chilian W, Chen YR, et al. Measurement of reactive oxygen species, reactive nitrogen species, and redox-dependent signaling in the cardiovascular system: a scientific statement from the American Heart Association. Circ Res. 2016;119:e39–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Lee R, Margaritis M, Channon KM, Antoniades C. Evaluating oxidative stress in human cardiovascular disease: methodological aspects and considerations. Curr Med Chem. 2012;19:2504–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Mason RP. Imaging free radicals in organelles, cells, tissue, and in vivo with immuno-spin trapping. Redox Biol. 2016;8:422–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Kalyanaraman B, Dranka BP, Hardy M, Michalski R, Zielonka J. HPLC-based monitoring of products formed from hydroethidine-based fluorogenic probes–the ultimate approach for intra- and extracellular superoxide detection. Biochim Biophys Acta. 2014;1840:739–44.

    Article  CAS  PubMed  Google Scholar 

  43. Robinson KM, Janes MS, Pehar M, Monette JS, Ross MF, Hagen TM, et al. Selective fluorescent imaging of superoxide in vivo using ethidium-based probes. Proc Natl Acad Sci USA. 2006;103:15038–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Murphy MP. How mitochondria produce reactive oxygen species. Biochem J. 2009;417:1–13.

    Article  CAS  PubMed  Google Scholar 

  45. Bleier L, Drose S. Superoxide generation by complex III: from mechanistic rationales to functional consequences. Biochim Biophys Acta. 2013;1827:1320–31.

    Article  CAS  PubMed  Google Scholar 

  46. Wong HS, Dighe PA, Mezera V, Monternier PA, Brand MD. Production of superoxide and hydrogen peroxide from specific mitochondrial sites under different bioenergetic conditions. J Biol Chem. 2017;292:16804–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Daiber A, Di Lisa F, Oelze M, Kröller-Schön S, Steven S, Schulz E, et al. Crosstalk of mitochondria with NADPH oxidase via reactive oxygen and nitrogen species signalling and its role for vascular function. Br J Pharm. 2017;174:1670–89.

    Article  CAS  Google Scholar 

  48. Li H, Han W, Villar VA, Keever LB, Lu Q, Hopfer U, et al. D1-like receptors regulate NADPH oxidase activity and subunit expression in lipid raft microdomains of renal proximal tubule cells. Hypertension. 2009;53:1054–61.

    Article  CAS  PubMed  Google Scholar 

  49. Yang S, Yang Y, Yu P, Yang J, Jiang X, Villar VA, et al. Dopamine D1 and D5 receptors differentially regulate oxidative stress through paraoxonase 2 in kidney cells. Free Radic Res. 2015;49:397–410.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Sulaiman D, Li J, Devarajan A, Cunningham CM, Li M, Fishbein GA, et al. Paraoxonase 2 protects against acute myocardial ischemia-reperfusion injury by modulating mitochondrial function and oxidative stress via the PI3K/Akt/GSK-3β RISK pathway. J Mol Cell Cardiol. 2019;129:154–64.

    Article  CAS  PubMed  Google Scholar 

  51. Li Z, Ji X, Wang W, Liu J, Liang X, Wu H, et al. Ammonia induces autophagy through dopamine receptor D3 and mTOR. PLoS ONE. 2016;11:e0153526.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Shin JH, Park SJ, Kim ES, Jo YK, Hong J, Cho DH. Sertindole, a potent antagonist at dopamine D2 receptors, induces autophagy by increasing reactive oxygen species in SH-SY5Y neuroblastoma cells. Biol Pharm Bull. 2012;35:1069–75.

    Article  CAS  PubMed  Google Scholar 

  53. Yan H, Li WL, Xu JJ, Zhu SQ, Long X, Che JP. D2 dopamine receptor antagonist raclopride induces non-canonical autophagy in cardiac myocytes. J Cell Biochem. 2013;114:103–10.

    Article  CAS  PubMed  Google Scholar 

  54. Dolma S, Selvadurai HJ, Lan X, Lee L, Kushida M, Voisin V, et al. Inhibition of dopamine receptor D4 impedes autophagic flux, proliferation, and survival of glioblastoma stem cells. Cancer Cell. 2016;29:859–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Jose PA, Eisner GM, Drago J, Carey RM, Felder RA. Dopamine receptor signaling defects in spontaneous hypertension. Am J Hypertens. 1996;9:400–5.

    Article  CAS  PubMed  Google Scholar 

  56. Missale C, Nash SR, Robinson SW, Jaber M, Caron MG. Dopamine receptors: from structure to function. Physiol Rev. 1998;78:189–225.

    Article  CAS  PubMed  Google Scholar 

  57. Gildea JJ, Shah I, Weiss R, Casscells ND, McGrath HE, Zhang J, et al. HK-2 human renal proximal tubule cells as a model for G protein-coupled receptor kinase type 4-mediated dopamine 1 receptor uncoupling. Hypertension. 2010;56:505–11.

    Article  CAS  PubMed  Google Scholar 

  58. Lee J, Giordano S, Zhang J. Autophagy, mitochondria and oxidative stress: cross-talk and redox signalling. Biochem J. 2012;441:523–40.

    Article  CAS  PubMed  Google Scholar 

  59. Pyo JO, Nah J, Kim HJ, Lee HJ, Heo J, Lee H, et al. Compensatory activation of ERK1/2 in Atg5-deficient mouse embryo fibroblasts suppresses oxidative stress-induced cell death. Autophagy. 2008;4:315–21.

    Article  CAS  PubMed  Google Scholar 

  60. Tian Y, Kuo CF, Sir D, Wang L, Govindarajan S, Petrovic LM, et al. Autophagy inhibits oxidative stress and tumor suppressors to exert its dual effect on hepatocarcinogenesis. Cell Death Differ. 2015;22:1025–34.

    Article  CAS  PubMed  Google Scholar 

  61. Diakopoulos KN, Lesina M, Wormann S, Song L, Aichler M, Schild L, et al. Impaired autophagy induces chronic atrophic pancreatitis in mice via sex- and nutrition-dependent processes. Gastroenterology. 2015;148:626–38.

    Article  PubMed  Google Scholar 

  62. Harada S, Nakagawa T, Yokoe S, Edogawa S, Takeuchi T, Inoue T, et al. Autophagy deficiency diminishes indomethacin-induced intestinal epithelial cell damage through activation of the ERK/Nrf2/HO-1 pathway. J Pharm Exp Ther. 2015;355:353–61.

    Article  CAS  Google Scholar 

  63. Jones DC, Gunasekar PG, Borowitz JL, Isom GE. Dopamine-induced apoptosis is mediated by oxidative stress and is enhanced by cyanide in differentiated PC12 cells. J Neurochem. 2000;74:2296–304.

    Article  CAS  PubMed  Google Scholar 

  64. Leng ZG, Lin SJ, Wu ZR, Guo YH, Cai L, Shang HB, et al. Activation of DRD5 (dopamine receptor D5) inhibits tumor growth by autophagic cell death. Autophagy. 2017;13:1404–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Yadav A, Vallabu S, Arora S, Tandon P, Slahan D, Teichberg S, et al. Ang II promotes autophagy in podocytes. Am J Physiol Cell Physiol. 2010;299:C488–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Sachse A, Wolf G. Angiotensin II-induced reactive oxygen species and the kidney. J Am Soc Nephrol. 2007;18:2439–46.

    Article  CAS  PubMed  Google Scholar 

  67. Zeng C, Yang Z, Wang Z, Jones J, Wang X, Altea J, et al. Interaction of angiotensin II type 1 and D5 dopamine receptors in renal proximal tubule cells. Hypertension. 2005;45:804–10.

    Article  CAS  PubMed  Google Scholar 

  68. Haller M, Hock AK, Giampazolias E, Oberst A, Green DR, Debnath J, et al. Ubiquitination and proteasomal degradation of ATG12 regulates its proapoptotic activity. Autophagy. 2014;10:2269–78.

    Article  CAS  PubMed  Google Scholar 

  69. Jiang S, Park DW, Gao Y, Ravi S, Darley-Usmar V, Abraham E, et al. Participation of proteasome-ubiquitin protein degradation in autophagy and the activation of amp-activated protein kinase. Cell Signal. 2015;27:1186–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Livnat-Levanon N, Glickman MH. Ubiquitin-proteasome system and mitochondria - reciprocity. Biochim Biophys Acta. 2011;1809:80–7.

    Article  CAS  PubMed  Google Scholar 

  71. Omar B, Zmuda-Trzebiatowska E, Manganiello V, Göransson O, Degerman E. Regulation of AMP-activated protein kinase by cAMP in adipocytes: roles for phosphodiesterases, protein kinase B, protein kinase A, Epac and lipolysis. Cell Signal. 2009;21:760–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Decara J, Rivera P, Arrabal S, Vargas A, Serrano A, Pavón FJ, et al. Cooperative role of the glucagon-like peptide-1 receptor and β3-adrenergic-mediated signalling on fat mass reduction through the downregulation of PKA/AKT/AMPK signalling in the adipose tissue and muscle of rats. Acta Physiol. 2018;222:e13008.

    Article  CAS  Google Scholar 

  73. Valsecchi F, Ramos-Espiritu LS, Buck J, Levin LR, Manfredi G. cAMP and mitochondria. Physiology. 2013;28:199–209.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Torres-Quiroz F, Filteau M, Landry CR. Feedback regulation between autophagy and PKA. Autophagy. 2015;11:1181–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Lee YJ, Shu MS, Kim JY, Kim YH, Sim KH, Sung WJ, et al. Cilostazol protects hepatocytes against alcohol-induced apoptosis via activation of AMPK pathway. PLoS ONE. 2019;14:e0211415.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Chen ML, Yi L, Jin X, Liang XY, Zhou Y, Zhang T, et al. Resveratrol attenuates vascular endothelial inflammation by inducing autophagy through the cAMP signaling pathway. Autophagy. 2013;9:2033–45.

    Article  CAS  PubMed  Google Scholar 

  77. Akabane S, Uno M, Tani N, Shimazaki S, Ebara N, Kato H, et al. PKA regulates PINK1 stability and parkin recruitment to damaged mitochondria through phosphorylation of MIC60. Mol Cell. 2016;62:371–84.

    Article  CAS  PubMed  Google Scholar 

  78. Wolter S, Kloth C, Golombek M, Dittmar F, Försterling L, Seifert R. cCMP causes caspase-dependent apoptosis in mouse lymphoma cell lines. Biochem Pharm. 2015;98:119–31.

    Article  CAS  PubMed  Google Scholar 

  79. Yu P, Sun M, Villar VA, Zhang Y, Weinman EJ, Felder RA, et al. Differential dopamine receptor subtype regulation of adenylyl cyclases in lipid rafts in human embryonic kidney and renal proximal tubule cells. Cell Signal. 2014;26:2521–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This study was supported in part by grants from the National Institutes of Health (HL074940, HL023081, DK039308, HL092196, DK119652, and DK090918), the Children’s National Medical Center Intramural Avery Award, the National Natural Science Foundation of China (81670698, 91739119, 81670406, 30971186), the Second Hospital of Dalian Medical University Start-up Funds, and the Department of Education of Liaoning Province Grant (L2016020).

Author information

Authors and Affiliations

  1. Department of Medicine, School of Medicine & Health Sciences, George Washington University, Washington, DC, USA

    Hewang Lee, Selim Rozyyev, Ines Armando & Pedro A. Jose

  2. Institute of Heart and Vessel Diseases, Affiliated Second Hospital, Dalian Medical University, Dalian, China

    Hewang Lee, Imran Perwaiz, Jin Wang, Ying Wang & Peng Qu

  3. Division of Nephrology, Department of Medicine, School of Medicine, University of Maryland, Baltimore, MD, USA

    Hewang Lee, Peiying Yu, Ines Armando & Pedro A. Jose

  4. Center for Molecular Physiology Research, Children’s Research Institute, Children’s National Medical Center, Washington, DC, USA

    Hewang Lee, Peiying Yu, Ines Armando & Pedro A. Jose

  5. Department of Pediatrics, Georgetown University Medical Center, Washington, DC, USA

    Hewang Lee, Peiying Yu, Ines Armando & Pedro A. Jose

  6. Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, USA

    Hewang Lee

  7. Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences & Comparative Medicine Center, Peking Union Medical College, Beijing, China

    Xiaoliang Jiang & Zhiwei Yang

  8. Center for Molecular Medicine and Genetics and Cardiovascular Research Institute, School of Medicine, Wayne State University, Detroit, MI, USA

    Maik Hüttemann

  9. Department of Pathology, University of Virginia Health Sciences Center, Charlottesville, VA, USA

    Robin A. Felder

  10. Molecular Neuropharmacology Section, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA

    David R. Sibley

  11. Department of Anesthesiology, School of Medicine, University of Maryland, Baltimore, MD, USA

    Brian M. Polster

  12. Department of Pharmacology and Physiology, School of Medicine & Health Sciences, George Washington University, Washington, DC, USA

    Pedro A. Jose

Authors
  1. Hewang Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiaoliang Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Imran Perwaiz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Peiying Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jin Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ying Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Maik Hüttemann
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Robin A. Felder
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. David R. Sibley
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Brian M. Polster
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Selim Rozyyev
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Ines Armando
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Zhiwei Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Peng Qu
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Pedro A. Jose
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

HL and PAJ designed the experiments. HL, XJ, IP, PY, SR, JW, and YW performed the experiments. DRS supplied the mice. HL, PY, MH, RAF, BMP, IA, ZY, PQ, and PAJ interpreted the experimental results. HL and PAJ drafted the manuscript. All authors edited, revised, and approved the final manuscript.

Corresponding author

Correspondence to Pedro A. Jose.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lee, H., Jiang, X., Perwaiz, I. et al. Dopamine D5 receptor-mediated decreases in mitochondrial reactive oxygen species production are cAMP and autophagy dependent. Hypertens Res 44, 628–641 (2021). https://doi.org/10.1038/s41440-021-00646-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41440-021-00646-w

Keywords

This article is cited by

Search

Advanced search

Quick links