Skip to main content

Advertisement

SpringerLink
Log in

Inflammation in Salt-Sensitive Hypertension and Renal Damage

  • Inflammation and Cardiovascular Diseases (A Kirabo, Section Editor)
  • Published:
Current Hypertension Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Low-grade inflammation drives elevations in blood pressure (BP) and consequent target organ damage in diverse experimental models of hypertension. Here, we discuss recent advances elucidating immune-mediated mechanisms of BP elevation and associated target organ damage.

Recent Findings

Inflammatory mediators produced by immune cells or target organs act on the kidney, vasculature, skin, and nervous system to modulate hypertension. For example, cells of the innate immune system, including monocytes, neutrophils, and dendritic cells (DCs), can all promote BP elevation via actions in the vasculature and kidney. Macrophages expressing VEGF-C impact non-osmotic sodium storage in the skin that in turn regulates salt sensitivity. Within the adaptive immune system, activated T cells can secrete tumor necrosis factor-alpha (TNF-α), interleukin-17a (IL-17a), and interferon-gamma (IFN-γ), each of which has augmented BP and renal damage in pre-clinical models. Inversely, deficiency of IL-17a in mice blunts the hypertensive response and attenuates renal sodium retention via a serum- and glucocorticoid-regulated kinase 1 (SGK1)–dependent pathway. Linking innate and adaptive immune responses, dendritic cells activated by augmented extracellular sodium concentrations stimulate T lymphocytes to produce pro-hypertensive cytokines. By contrast, regulatory T cells (Tregs) can protect against hypertension and associated kidney injury.

Summary

Rodent studies reveal diverse mechanisms via which cells of the innate and adaptive immune systems drive blood pressure elevation by altering the inflammatory milieu in the kidney, vasculature, and brain.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Collaboration NCDRF. Worldwide trends in blood pressure from 1975 to 2015: a pooled analysis of 1479 population-based measurement studies with 19.1 million participants. Lancet. 2017;389(10064):37–55. https://doi.org/10.1016/S0140-6736(16)31919-5.

    Article  Google Scholar 

  2. Egan BM, Zhao Y, Axon R. US trends in prevalence, awareness, treatment, and control of hypertension, 1988–2008. JAMA. 2010;303(20):2043–50. https://doi.org/10.1001/jama.2010.650.

    Article  CAS  PubMed  Google Scholar 

  3. Caillon A, Schiffrin EL. Role of inflammation and immunity in hypertension: recent epidemiological, laboratory, and Clinical Evidence. Curr Hypertens Rep. 2016;18(3):21. https://doi.org/10.1007/s11906-016-0628-7.

    Article  PubMed  Google Scholar 

  4. Norlander AE, Madhur MS, Harrison DG. The immunology of hypertension. J Exp Med. 2018;215(1):21–33. https://doi.org/10.1084/jem.20171773.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Muller DN, Shagdarsuren E, Park JK, Dechend R, Mervaala E, Hampich F, et al. Immunosuppressive treatment protects against angiotensin II-induced renal damage. Am J Pathol. 2002;161(5):1679–93. https://doi.org/10.1016/S0002-9440(10)64445-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Rodriguez-Iturbe B, Pons H, Quiroz Y, Gordon K, Rincon J, Chavez M, et al. Mycophenolate mofetil prevents salt-sensitive hypertension resulting from angiotensin II exposure. Kidney Int. 2001;59(6):2222–32.

    Article  CAS  PubMed  Google Scholar 

  7. Ko EA, Amiri F, Pandey NR, Javeshghani D, Leibovitz E, Touyz RM, et al. Resistance artery remodeling in deoxycorticosterone acetate-salt hypertension is dependent on vascular inflammation: evidence from m-CSF-deficient mice. Am J Physiol Heart Circ Physiol. 2007;292(4):H1789–95. https://doi.org/10.1152/ajpheart.01118.2006.

    Article  CAS  PubMed  Google Scholar 

  8. Kossmann S, Hu H, Steven S, Schonfelder T, Fraccarollo D, Mikhed Y, et al. Inflammatory monocytes determine endothelial nitric-oxide synthase uncoupling and nitro-oxidative stress induced by angiotensin II. J Biol Chem. 2014;289(40):27540–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Wiig H, Schroder A, Neuhofer W, Jantsch J, Kopp C, Karlsen TV, et al. Immune cells control skin lymphatic electrolyte homeostasis and blood pressure. J Clin Invest. 2013;123(7):2803–15. https://doi.org/10.1172/JCI60113.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Xiao L, Kirabo A, Wu J, Saleh MA, Zhu L, Wang F, et al. Renal denervation prevents immune cell activation and renal inflammation in angiotensin II-induced hypertension. Circ Res. 2015;117(6):547–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Zaldivia MTK, Rivera J, Hering D, Marusic P, Sata Y, Lim B, et al. Renal denervation reduces monocyte activation and monocyte-platelet aggregate formation: an anti-inflammatory effect relevant for cardiovascular risk. Hypertension. 2017;69(2):323–31.

    Article  CAS  PubMed  Google Scholar 

  12. O’Donnell M, Mente A, Yusuf S. Sodium intake and cardiovascular health. Circ Res. 2015;116(6):1046–57.

    Article  PubMed  Google Scholar 

  13. Wright JT Jr, Rahman M, Scarpa A, Fatholahi M, Griffin V, Jean-Baptiste R, et al. Determinants of salt sensitivity in black and white normotensive and hypertensive women. Hypertension. 2003;42(6):1087–92.

    Article  CAS  PubMed  Google Scholar 

  14. Chen J, Gu D, Huang J, Rao DC, Jaquish CE, Hixson JE, et al. Metabolic syndrome and salt sensitivity of blood pressure in non-diabetic people in China: a dietary intervention study. Lancet. 2009;373(9666):829–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Gradin K, Persson B. Chronic salt loading and adrenergic mechanisms in the Sprague-Dawley rat. Pharmacol Toxicol. 1987;60(4):299–304.

    Article  CAS  PubMed  Google Scholar 

  16. Mattson DL, James L, Berdan EA, Meister CJ. Immune suppression attenuates hypertension and renal disease in the Dahl salt-sensitive rat. Hypertension. 2006;48(1):149–56.

    Article  CAS  PubMed  Google Scholar 

  17. Crowley SD, Song Y-S, Lin EE, Griffiths R, Kim H-S, Ruiz P. Lymphocyte responses exacerbate angiotensin II-dependent hypertension. Am J Phys Regul Integr Comp Phys. 2010;298(4):R1089–97.

    CAS  Google Scholar 

  18. Norlander AE, Saleh MA, Kamat NV, Ko B, Gnecco J, Zhu L, et al. Interleukin-17A regulates renal sodium transporters and renal injury in angiotensin II-induced hypertension. Hypertension. 2016;68(1):167–74.

    Article  CAS  PubMed  Google Scholar 

  19. Wade B, Petrova G, Mattson DL. Role of immune factors in angiotensin II-induced hypertension and renal damage in Dahl salt-sensitive rats. Am J Phys Regul Integr Comp Phys. 2018;314(3):R323–R33.

    Google Scholar 

  20. Wenzel P, Knorr M, Kossmann S, Stratmann J, Hausding M, Schuhmacher S, et al. Lysozyme M-positive monocytes mediate angiotensin II-induced arterial hypertension and vascular dysfunction. Circulation. 2011;124(12):1370–81.

    Article  CAS  PubMed  Google Scholar 

  21. Chatterjee M, Saluja R, Tewari S, Barthwal MK, Goel SK, Dikshit M. Augmented nitric oxide generation in neutrophils: oxidative and pro-inflammatory implications in hypertension. Free Radic Res. 2009;43(12):1195–204.

    Article  CAS  PubMed  Google Scholar 

  22. Kirabo A, Fontana V, de Faria APC, Loperena R, Galindo CL, Wu J, et al. DC isoketal-modified proteins activate T cells and promote hypertension. J Clin Invest. 2014;124(10):4642–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Machnik A, Neuhofer W, Jantsch J, Dahlmann A, Tammela T, Machura K, et al. Macrophages regulate salt-dependent volume and blood pressure by a vascular endothelial growth factor-C-dependent buffering mechanism. Nat Med. 2009;15(5):545–52. https://doi.org/10.1038/nm.1960.

    Article  CAS  PubMed  Google Scholar 

  24. Zhang MZ, Yao B, Wang Y, Yang S, Wang S, Fan X, et al. Inhibition of cyclooxygenase-2 in hematopoietic cells results in salt-sensitive hypertension. J Clin Invest. 2015;125(11):4281–94. https://doi.org/10.1172/JCI81550.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Chan CT, Sobey CG, Lieu M, Ferens D, Kett MM, Diep H, et al. Obligatory role for B cells in the development of angiotensin II-dependent hypertension. Hypertension. 2015;66(5):1023–33. https://doi.org/10.1161/HYPERTENSIONAHA.115.05779.

    Article  CAS  PubMed  Google Scholar 

  26. Guzik TJ, Hoch NE, Brown KA, McCann LA, Rahman A, Dikalov S, et al. Role of the T cell in the genesis of angiotensin II induced hypertension and vascular dysfunction. J Exp Med. 2007;204(10):2449–60. https://doi.org/10.1084/jem.20070657.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. De Miguel C, Guo C, Lund H, Feng D, Mattson DL. Infiltrating T lymphocytes in the kidney increase oxidative stress and participate in the development of hypertension and renal disease. Am J Physiol Ren Physiol. 2011;300(3):F734–42.

    Article  Google Scholar 

  28. Lloyd-Sherlock P, Beard J, Minicuci N, Ebrahim S, Chatterji S. Hypertension among older adults in low- and middle-income countries: prevalence, awareness and control. Int J Epidemiol. 2014;43(1):116–28.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Rafey MA. Resistant hypertension in the elderly. Clin Geriatr Med. 2009;25(2):289–301.

    Article  PubMed  Google Scholar 

  30. Bautista LE, Vera LM, Arenas IA, Gamarra G. Independent association between inflammatory markers (C-reactive protein, interleukin-6, and TNF-alpha) and essential hypertension. J Hum Hypertens. 2005;19(2):149–54.

    Article  CAS  PubMed  Google Scholar 

  31. Chae CU, Lee RT, Rifai N, Ridker PM. Blood pressure and inflammation in apparently healthy men. Hypertension. 2001;38(3):399–403.

    Article  CAS  PubMed  Google Scholar 

  32. Dalekos GN, Elisaf M, Bairaktari E, Tsolas O, Siamopoulos KC. Increased serum levels of interleukin-1beta in the systemic circulation of patients with essential hypertension: additional risk factor for atherogenesis in hypertensive patients? J Lab Clin Med. 1997;129(3):300–8.

    Article  CAS  PubMed  Google Scholar 

  33. Yu X, Yang Z, Yu M. Correlation of tumor necrosis factor alpha and interleukin 6 with hypertensive renal damage. Ren Fail. 2010;32(4):475–9.

    Article  PubMed  Google Scholar 

  34. Hu J, Zhu Q, Xia M, Guo TL, Wang Z, Li P-L, et al. Transplantation of mesenchymal stem cells into the renal medulla attenuated salt-sensitive hypertension in Dahl S rat. J Mol Med. 2014;92(11):1139–45.

    Article  CAS  PubMed  Google Scholar 

  35. Sriramula S, Haque M, Majid DS, Francis J. Involvement of tumor necrosis factor-alpha in angiotensin II-mediated effects on salt appetite, hypertension, and cardiac hypertrophy. Hypertension. 2008;51(5):1345–51. https://doi.org/10.1161/HYPERTENSIONAHA.107.102152.

    Article  CAS  PubMed  Google Scholar 

  36. Madhur MS, Lob HE, McCann LA, Iwakura Y, Blinder Y, Guzik TJ, et al. Interleukin 17 promotes angiotensin II-induced hypertension and vascular dysfunction. Hypertension. 2010;55(2):500–7. https://doi.org/10.1161/HYPERTENSIONAHA.109.145094.

    Article  CAS  PubMed  Google Scholar 

  37. Kamat NV, Thabet SR, Xiao L, Saleh MA, Kirabo A, Madhur MS, et al. Renal transporter activation during angiotensin-II hypertension is blunted in interferon-gamma−/− and interleukin-17A−/− mice. Hypertension. 2015;65(3):569–76.

    Article  CAS  PubMed  Google Scholar 

  38. Zhang W, Wang W, Yu H, Zhang Y, Dai Y, Ning C, et al. Interleukin 6 underlies angiotensin II-induced hypertension and chronic renal damage. Hypertension. 2012;59(1):136–44. https://doi.org/10.1161/HYPERTENSIONAHA.111.173328.

    Article  CAS  PubMed  Google Scholar 

  39. Lepone LM, Donahue RN, Grenga I, Metenou S, Richards J, Heery CR, et al. Analyses of 123 peripheral human immune cell subsets: defining differences with age and between healthy donors and cancer patients not detected in analysis of standard immune cell types. J Circ Biomark. 2016;5:5.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Striz I, Brabcova E, Kolesar L, Sekerkova A. Cytokine networking of innate immunity cells: a potential target of therapy. Clin Sci (Lond). 2014;126(9):593–612.

    Article  CAS  Google Scholar 

  41. Cochain C, Koch M, Chaudhari SM, Busch M, Pelisek J, Boon L, et al. CD8+ T cells regulate monopoiesis and circulating Ly6C-high monocyte levels in atherosclerosis in mice. Circ Res. 2015;117(3):244–53.

    Article  CAS  PubMed  Google Scholar 

  42. Gallego A, Vargas JA, Castejon R, Citores MJ, Romero Y, Millan I, et al. Production of intracellular IL-2, TNF-alpha, and IFN-gamma by T cells in B-CLL. Cytometry B Clin Cytom. 2003;56(1):23–9.

    Article  CAS  PubMed  Google Scholar 

  43. Kelly BL, Locksley RM. Coordinate regulation of the IL-4, IL-13, and IL-5 cytokine cluster in Th2 clones revealed by allelic expression patterns. J Immunol. 2000;165(6):2982–6.

    Article  CAS  PubMed  Google Scholar 

  44. Ma H-L, Napierata L, Stedman N, Benoit S, Collins M, Nickerson-Nutter C, et al. Tumor necrosis factor alpha blockade exacerbates murine psoriasis-like disease by enhancing Th17 function and decreasing expansion of Treg cells. Arthritis Rheum. 2010;62(2):430–40.

    Article  CAS  PubMed  Google Scholar 

  45. Haque R, Lei F, Xiong X, Bian Y, Zhao B, Wu Y, et al. Programming of regulatory T cells from pluripotent stem cells and prevention of autoimmunity. J Immunol. 2012;189(3):1228–36.

    Article  CAS  PubMed  Google Scholar 

  46. Ballou SP, Lozanski G. Induction of inflammatory cytokine release from cultured human monocytes by C-reactive protein. Cytokine. 1992;4(5):361–8.

    Article  CAS  PubMed  Google Scholar 

  47. Loperena R, Van Beusecum JP, Itani HA, Engel N, Laroumanie F, Xiao L, et al. Hypertension and increased endothelial mechanical stretch promote monocyte differentiation and activation: roles of STAT3, interleukin 6 and hydrogen peroxide. Cardiovasc Res. 2018;114(11):1547–63.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Shen K, DeLano FA, Zweifach BW, Schmid-Schonbein GW. Circulating leukocyte counts, activation, and degranulation in Dahl hypertensive rats. Circ Res. 1995;76(2):276–83.

    Article  CAS  PubMed  Google Scholar 

  49. Artigues C, Richard V, Roussel C, Lallemand F, Henry JP, Thuillez C. Increased endothelium--monocyte interactions in salt-sensitive hypertension: effect of L-arginine. J Cardiovasc Pharmacol. 2000;35(3):468–73.

    Article  CAS  PubMed  Google Scholar 

  50. Beswick RA, Zhang H, Marable D, Catravas JD, Hill WD, Webb RC. Long-term antioxidant administration attenuates mineralocorticoid hypertension and renal inflammatory response. Hypertension. 2001;37(2 Pt 2):781–6.

    Article  CAS  PubMed  Google Scholar 

  51. Rocha R, Rudolph AE, Frierdich GE, Nachowiak DA, Kekec BK, Blomme EA, et al. Aldosterone induces a vascular inflammatory phenotype in the rat heart. Am J Physiol Heart Circ Physiol. 2002;283(5):H1802–10. https://doi.org/10.1152/ajpheart.01096.2001.

    Article  CAS  PubMed  Google Scholar 

  52. Blasi ER, Rocha R, Rudolph AE, Blomme EA, Polly ML, McMahon EG. Aldosterone/salt induces renal inflammation and fibrosis in hypertensive rats. Kidney Int. 2003;63(5):1791–800. https://doi.org/10.1046/j.1523-1755.2003.00929.x.

    Article  CAS  PubMed  Google Scholar 

  53. Vieira JM Jr, Rodrigues LT, Mantovani E, Delle H, Mattar AL, Malheiros DM, et al. Statin monotherapy attenuates renal injury in a salt-sensitive hypertension model of renal disease. Nephron Physiol. 2005;101(4):p82–91. https://doi.org/10.1159/000087576.

    Article  CAS  PubMed  Google Scholar 

  54. Tian N, Gu JW, Jordan S, Rose RA, Hughson MD, Manning RD,J. Immune suppression prevents renal damage and dysfunction and reduces arterial pressure in salt-sensitive hypertension. Am J Physiol Heart Circ Physiol. 2007;292(2):H1018–25. https://doi.org/10.1152/ajpheart.00487.2006.

    Article  CAS  PubMed  Google Scholar 

  55. De Ciuceis C, Amiri F, Brassard P, Endemann DH, Touyz RM, Schiffrin EL. Reduced vascular remodeling, endothelial dysfunction, and oxidative stress in resistance arteries of angiotensin II-infused macrophage colony-stimulating factor-deficient mice: evidence for a role in inflammation in angiotensin-induced vascular injury. Arterioscler Thromb Vasc Biol. 2005;25(10):2106–13. https://doi.org/10.1161/01.ATV.0000181743.28028.57.

    Article  CAS  PubMed  Google Scholar 

  56. Huang L, Wang A, Hao Y, Li W, Liu C, Yang Z, et al. Macrophage depletion lowered blood pressure and attenuated hypertensive renal injury and fibrosis. Front Physiol. 2018;9:473.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Thang LV, Demel SL, Crawford R, Kaminski NE, Swain GM, Van Rooijen N, et al. Macrophage depletion lowers blood pressure and restores sympathetic nerve alpha2-adrenergic receptor function in mesenteric arteries of DOCA-salt hypertensive rats. Am J Physiol Heart Circ Physiol. 2015;309(7):H1186–97. https://doi.org/10.1152/ajpheart.00283.2015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Machnik A, Dahlmann A, Kopp C, Goss J, Wagner H, van Rooijen N, et al. Mononuclear phagocyte system depletion blocks interstitial tonicity-responsive enhancer binding protein/vascular endothelial growth factor C expression and induces salt-sensitive hypertension in rats. Hypertension. 2010;55(3):755–61. https://doi.org/10.1161/HYPERTENSIONAHA.109.143339.

    Article  CAS  PubMed  Google Scholar 

  59. Fabbiano S, Menacho-Marquez M, Robles-Valero J, Pericacho M, Matesanz-Marin A, Garcia-Macias C, et al. Immunosuppression-independent role of regulatory T cells against hypertension-driven renal dysfunctions. Mol Cell Biol. 2015;35(20):3528–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Liu X, Zhang Q, Wu H, Du H, Liu L, Shi H, et al. Blood neutrophil to lymphocyte ratio as a predictor of hypertension. Am J Hypertens. 2015;28(11):1339–46.

    Article  CAS  PubMed  Google Scholar 

  61. Tatsukawa Y, Hsu W-L, Yamada M, Cologne JB, Suzuki G, Yamamoto H, et al. White blood cell count, especially neutrophil count, as a predictor of hypertension in a Japanese population. Hypertens Res. 2008;31(7):1391–7.

    Article  PubMed  Google Scholar 

  62. Kossmann S, Schwenk M, Hausding M, Karbach SH, Schmidgen MI, Brandt M, et al. Angiotensin II-induced vascular dysfunction depends on interferon-gamma-driven immune cell recruitment and mutual activation of monocytes and NK-cells. Arterioscler Thromb Vasc Biol. 2013;33(6):1313–9. https://doi.org/10.1161/ATVBAHA.113.301437.

    Article  CAS  PubMed  Google Scholar 

  63. Vinh A, Chen W, Blinder Y, Weiss D, Taylor WR, Goronzy JJ, et al. Inhibition and genetic ablation of the B7/CD28 T-cell costimulation axis prevents experimental hypertension. Circulation. 2010;122(24):2529–37.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Itani HA, Xiao L, Saleh MA, Wu J, Pilkinton MA, Dale BL, et al. CD70 exacerbates blood pressure elevation and renal damage in response to repeated hypertensive stimuli. Circ Res. 2016;118(8):1233–43. https://doi.org/10.1161/CIRCRESAHA.115.308111.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Barbaro NR, Foss JD, Kryshtal DO, Tsyba N, Kumaresan S, Xiao L, et al. Dendritic cell amiloride-sensitive channels mediate sodium-induced inflammation and hypertension. Cell Rep. 2017;21(4):1009–20. https://doi.org/10.1016/j.celrep.2017.10.002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Hevia D, Araos P, Prado C, Fuentes Luppichini E, Rojas M, Alzamora R, et al. Myeloid CD11c(+) antigen-presenting cells ablation prevents hypertension in response to angiotensin II plus high-salt diet. Hypertension. 2018;71(4):709–18. https://doi.org/10.1161/HYPERTENSIONAHA.117.10145.

    Article  CAS  PubMed  Google Scholar 

  67. Svendsen UG. Evidence for an initial, thymus independent and a chronic, thymus dependent phase of DOCA and salt hypertension in mice. Acta Pathol Microbiol Scand A. 1976;84(6):523–8.

    CAS  PubMed  Google Scholar 

  68. Crowley SD, Frey CW, Gould SK, Griffiths R, Ruiz P, Burchette JL, et al. Stimulation of lymphocyte responses by angiotensin II promotes kidney injury in hypertension. Am J Physiol Renal Physiol. 2008;295(2):F515–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. De Miguel C, Das S, Lund H, Mattson DL. T lymphocytes mediate hypertension and kidney damage in Dahl salt-sensitive rats. Am J Physiol Regul Integr Comp Physiol. 2010;298(4):R1136–42.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Abais-Battad JM, Lund H, Fehrenbach DJ, Dasinger JH, Mattson DL. Rag1-null Dahl SS rats reveal that adaptive immune mechanisms exacerbate high protein-induced hypertension and renal injury. Am J Physiol Regul Integr Comp Physiol. 2018;315(1):R28–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Youn JC, Yu HT, Lim BJ, Koh MJ, Lee J, Chang DY, et al. Immunosenescent CD8+ T cells and C-X-C chemokine receptor type 3 chemokines are increased in human hypertension. Hypertension. 2013;62(1):126–33. https://doi.org/10.1161/HYPERTENSIONAHA.113.00689.

    Article  CAS  PubMed  Google Scholar 

  72. Kvakan H, Kleinewietfeld M, Qadri F, Park JK, Fischer R, Schwarz I, et al. Regulatory T cells ameliorate angiotensin II-induced cardiac damage. Circulation. 2009;119(22):2904–12. https://doi.org/10.1161/CIRCULATIONAHA.108.832782.

    Article  CAS  PubMed  Google Scholar 

  73. Barhoumi T, Kasal DA, Li MW, Shbat L, Laurant P, Neves MF, et al. T regulatory lymphocytes prevent angiotensin II-induced hypertension and vascular injury. Hypertension. 2011;57(3):469–76. https://doi.org/10.1161/HYPERTENSIONAHA.110.162941.

    Article  CAS  PubMed  Google Scholar 

  74. Kasal DA, Barhoumi T, Li MW, Yamamoto N, Zdanovich E, Rehman A, et al. T regulatory lymphocytes prevent aldosterone-induced vascular injury. Hypertension. 2012;59(2):324–30. https://doi.org/10.1161/HYPERTENSIONAHA.111.181123.

    Article  CAS  PubMed  Google Scholar 

  75. Mian MO, Barhoumi T, Briet M, Paradis P, Schiffrin EL. Deficiency of T-regulatory cells exaggerates angiotensin II-induced microvascular injury by enhancing immune responses. J Hypertens. 2016;34(1):97–108. https://doi.org/10.1097/HJH.0000000000000761.

    Article  CAS  PubMed  Google Scholar 

  76. Chen XH, Ruan CC, Ge Q, Ma Y, Xu JZ, Zhang ZB, et al. Deficiency of complement C3a and C5a receptors prevents angiotensin II-induced hypertension via regulatory T cells. Circ Res. 2018;122(7):970–83. https://doi.org/10.1161/CIRCRESAHA.117.312153.

    Article  CAS  PubMed  Google Scholar 

  77. Hernandez AL, Kitz A, Wu C, Lowther DE, Rodriguez DM, Vudattu N, et al. Sodium chloride inhibits the suppressive function of FOXP3+ regulatory T cells. J Clin Invest. 2015;125(11):4212–22. https://doi.org/10.1172/JCI81151.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Caillon A, Mian MOR, Fraulob-Aquino JC, Huo K-G, Barhoumi T, Ouerd S, et al. Gammadelta T cells mediate angiotensin II-induced hypertension and vascular injury. Circulation. 2017;135(22):2155–62.

    Article  CAS  PubMed  Google Scholar 

  79. Kleinewietfeld M, Manzel A, Titze J, Kvakan H, Yosef N, Linker RA, et al. Sodium chloride drives autoimmune disease by the induction of pathogenic TH17 cells. Nature. 2013;496(7446):518–22. https://doi.org/10.1038/nature11868.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Wu C, Yosef N, Thalhamer T, Zhu C, Xiao S, Kishi Y, et al. Induction of pathogenic TH17 cells by inducible salt-sensing kinase SGK1. Nature. 2013;496(7446):513–7. https://doi.org/10.1038/nature11984.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Norlander AE, Saleh MA, Pandey AK, Itani HA, Wu J, Xiao L, et al. A salt-sensing kinase in T lymphocytes, SGK1, drives hypertension and hypertensive end-organ damage. JCI Insight. 2017;2(13).

  82. Saleh MA, Norlander AE, Madhur MS. Inhibition of interleukin 17-a but not interleukin-17F signaling lowers blood pressure and reduces end-organ inflammation in angiotensin II-induced hypertension. JACC Basic Transl Sci. 2016;1(7):606–16. https://doi.org/10.1016/j.jacbts.2016.07.009.

    Article  PubMed  PubMed Central  Google Scholar 

  83. Saleh MA, McMaster WG, Wu J, Norlander AE, Funt SA, Thabet SR, et al. Lymphocyte adaptor protein LNK deficiency exacerbates hypertension and end-organ inflammation. J Clin Invest. 2015;125(3):1189–202.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Ramseyer VD, Hong NJ, Garvin JL. Tumor necrosis factor alpha decreases nitric oxide synthase type 3 expression primarily via Rho/Rho kinase in the thick ascending limb. Hypertension. 2012;59(6):1145–50.

    Article  CAS  PubMed  Google Scholar 

  85. Zhang J, Patel MB, Griffiths R, Mao A, Song YS, Karlovich NS, et al. Tumor necrosis factor-alpha produced in the kidney contributes to angiotensin II-dependent hypertension. Hypertension. 2014;64(6):1275–81. https://doi.org/10.1161/HYPERTENSIONAHA.114.03863.

    Article  CAS  PubMed  Google Scholar 

  86. Ferreri NR, Escalante BA, Zhao Y, An SJ, McGiff JC. Angiotensin II induces TNF production by the thick ascending limb: functional implications. Am J Phys. 1998;274(1 Pt 2):F148–55.

    CAS  Google Scholar 

  87. Hashmat S, Rudemiller N, Lund H, Abais-Battad JM, Van Why S, Mattson DL. Interleukin-6 inhibition attenuates hypertension and associated renal damage in Dahl salt-sensitive rats. Am J Physiol Ren Physiol. 2016;311(3):F555–61.

    Article  CAS  Google Scholar 

  88. Brands MW, Banes-Berceli AKL, Inscho EW, Al-Azawi H, Allen AJ, Labazi H. Interleukin 6 knockout prevents angiotensin II hypertension: role of renal vasoconstriction and janus kinase 2/signal transducer and activator of transcription 3 activation. Hypertension. 2010;56(5):879–84.

    Article  CAS  PubMed  Google Scholar 

  89. Li K, Guo D, Zhu H, Hering-Smith KS, Hamm LL, Ouyang J, et al. Interleukin-6 stimulates epithelial sodium channels in mouse cortical collecting duct cells. Am J Physiol Regul Integr Comp Physiol. 2010;299(2):R590–5. https://doi.org/10.1152/ajpregu.00207.2009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Kassan M, Galan M, Partyka M, Trebak M, Matrougui K. Interleukin-10 released by CD4(+)CD25(+) natural regulatory T cells improves microvascular endothelial function through inhibition of NADPH oxidase activity in hypertensive mice. Arterioscler Thromb Vasc Biol. 2011;31(11):2534–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Liu Y, Rafferty TM, Rhee SW, Webber JS, Song L, Ko B, et al. CD8+ T cells stimulate Na-Cl co-transporter NCC in distal convoluted tubules leading to salt-sensitive hypertension. Nat Commun. 2017;8:14037.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Rodriguez-Iturbe B, Quiroz Y, Nava M, Bonet L, Chavez M, Herrera-Acosta J, et al. Reduction of renal immune cell infiltration results in blood pressure control in genetically hypertensive rats. Am J Physiol Ren Physiol. 2002;282(2):F191–201. https://doi.org/10.1152/ajprenal.0197.2001.

    Article  Google Scholar 

  93. Herrera J, Ferrebuz A, MacGregor EG, Rodriguez-Iturbe B. Mycophenolate mofetil treatment improves hypertension in patients with psoriasis and rheumatoid arthritis. J Am Soc Nephrol. 2006;17(12 Suppl 3):S218–25.

    Article  CAS  PubMed  Google Scholar 

  94. Hoorn EJ, Walsh SB, McCormick JA, Furstenberg A, Yang CL, Roeschel T, et al. The calcineurin inhibitor tacrolimus activates the renal sodium chloride cotransporter to cause hypertension. Nat Med. 2011;17(10):1304–9. https://doi.org/10.1038/nm.2497.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Bamoulid J, Staeck O, Halleck F, Khadzhynov D, Brakemeier S, Durr M, et al. The need for minimization strategies: current problems of immunosuppression. Transpl Int. 2015;28(8):891–900.

    Article  CAS  PubMed  Google Scholar 

  96. Kinlay S, Schwartz GG, Olsson AG, Rifai N, Leslie SJ, Sasiela WJ, et al. High-dose atorvastatin enhances the decline in inflammatory markers in patients with acute coronary syndromes in the MIRACL study. Circulation. 2003;108(13):1560–6. https://doi.org/10.1161/01.CIR.0000091404.09558.AF.

    Article  CAS  PubMed  Google Scholar 

  97. Strazzullo P, Kerry SM, Barbato A, Versiero M, D’Elia L, Cappuccio FP. Do statins reduce blood pressure?: a meta-analysis of randomized, controlled trials. Hypertension. 2007;49(4):792–8.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This work was supported by NIH grants DK087893, HL128355; Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development Grant BX000893.

Author information

Authors and Affiliations

  1. Division of Nephrology, Department of Medicine, Duke University and Durham VA Medical Centers, Durham, NC, 27710, USA

    Xiaohan Lu & Steven D. Crowley

Authors
  1. Xiaohan Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Steven D. Crowley
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Steven D. Crowley.

Ethics declarations

Conflict of Interest

The authors declare no conflicts of interest relevant to this manuscript.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Inflammation and Cardiovascular Diseases

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lu, X., Crowley, S.D. Inflammation in Salt-Sensitive Hypertension and Renal Damage. Curr Hypertens Rep 20, 103 (2018). https://doi.org/10.1007/s11906-018-0903-x

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11906-018-0903-x

Keywords

Search

Navigation