Skip to main content

Advertisement

SpringerLink
Log in

Is hypertension an immunologic disease?

  • Published:
Current Cardiology Reports Aims and scope Submit manuscript

Abstract

Several studies published in the past three decades have suggested that the adaptive immune system contributes to hypertension. Recent studies have shown that T cells play a crucial role in the blood pressure elevation caused by angiotensin II and in response to sodium and volume challenge. Hypertensive stimuli cause effector T cells to enter visceral fat, in particular perivascular fat, where they release cytokines that promote vasoconstriction. Similarly, effector T cells accumulate in the kidney in hypertension and contribute to renal dysfunction, promoting sodium and volume retention. These findings provide some insight into the relationship between inflammation and hypertension and suggest that efforts to reduce T-cell activation may be useful in preventing or treating this disease.

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

Similar content being viewed by others

References and Recommended Reading

  1. Shepherd JT: Franz Volhard lecture. Increased systemic vascular resistance and primary hypertension: the expanding complexity. J Hypertens Suppl 1990, 8:S15–S27.

    PubMed  CAS  Google Scholar 

  2. Garovic VD, Hilliard AA, Turner ST: Monogenic forms of low-renin hypertension. Nat Clin Pract Nephrol 2006, 2:624–630.

    Article  PubMed  CAS  Google Scholar 

  3. Crowley SD, Gurley SB, Herrera MJ, et al.: Angiotensin II causes hypertension and cardiac hypertrophy through its receptors in the kidney. Proc Natl Acad Sci U S A 2006, 103:17985–17990.

    Article  PubMed  CAS  Google Scholar 

  4. Mangiapane ML, Simpson JB: Subfornical organ: forebrain site of pressor and dipsogenic action of angiotensin II. Am J Physiol 1980, 239:R382–R389.

    PubMed  CAS  Google Scholar 

  5. Brody MJ: Central nervous system and mechanisms of hypertension. Clin Physiol Biochem 1988, 6:230–239.

    Article  PubMed  CAS  Google Scholar 

  6. Blake GJ, Rifai N, Buring JE, et al.: Blood pressure, C-reactive protein, and risk of future cardiovascular events. Circulation 2003, 108:2993–2999.

    Article  PubMed  CAS  Google Scholar 

  7. 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, 84:523–528.

    CAS  Google Scholar 

  8. Tian N, Gu JW, Jordan S, et al.: Immune suppression prevents renal damage and dysfunction and reduces arterial pressure in salt-sensitive hypertension. Am J Physiol Heart Circ Physiol 2007, 292:H1018–H1025.

    Article  PubMed  CAS  Google Scholar 

  9. Mattson DL, James L, Berdan EA, et al.: Immune suppression attenuates hypertension and renal disease in the Dahl salt-sensitive rat. Hypertension 2006, 48:149–156.

    Article  PubMed  CAS  Google Scholar 

  10. Bravo Y, Quiroz Y, Ferrebuz A, et al.: Mycophenolate mofetil administration reduces renal inflammation, oxidative stress, and arterial pressure in rats with lead-induced hypertension. Am J Physiol Renal Physiol 2007, 293:F616–F623.

    Article  PubMed  CAS  Google Scholar 

  11. Pechman KR, Basile DP, Lund H, et al.: Immune suppression blocks sodium-sensitive hypertension following recovery from ischemic acute renal failure. Am J Physiol Regul Integr Comp Physiol 2008, 294:R1234–R1239.

    PubMed  CAS  Google Scholar 

  12. Herrera J, Ferrebuz A, Macgregor EG, et al.: Mycophenolate mofetil treatment improves hypertension in patients with psoriasis and rheumatoid arthritis. J Am Soc Nephrol 2006, 17:S218–S225.

    Article  PubMed  CAS  Google Scholar 

  13. Panoulas VF, Douglas KM, Milionis HJ, et al.: Prevalence and associations of hypertension and its control in patients with rheumatoid arthritis. Rheumatology (Oxford) 2007, 46:1477–1482.

    Article  CAS  Google Scholar 

  14. Neimann AL, Shin DB, Wang X, et al.: Prevalence of cardiovascular risk factors in patients with psoriasis. J Am Acad Dermatol 2006, 55:829–835.

    Article  PubMed  Google Scholar 

  15. Matthiesen L, Berg G, Ernerudh J, et al.: Immunology of preeclampsia. Chem Immunol Allergy 2005, 89:49–61.

    Article  PubMed  CAS  Google Scholar 

  16. Mahmoud F, Omu A, Abul H, et al.: Lymphocyte subpopulations in pregnancy complicated by hypertension. J Obstet Gynaecol 2003, 23:20–26.

    Article  PubMed  Google Scholar 

  17. Franco M, Martinez F, Quiroz Y, et al.: Renal angiotensin II concentration and interstitial infiltration of immune cells are correlated with blood pressure levels in salt-sensitive hypertension. Am J Physiol 2007, 293:R251–R256.

    CAS  Google Scholar 

  18. Nava M, Quiroz Y, Vaziri N, et al.: Melatonin reduces renal interstitial inflammation and improves hypertension in spontaneously hypertensive rats. Am J Physiol Renal Physiol 2003, 284:F447–F454.

    PubMed  CAS  Google Scholar 

  19. Rodriguez-Iturbe B, Quiroz Y, Nava M, et al.: Reduction of renal immune cell infiltration results in blood pressure control in genetically hypertensive rats. Am J Physiol Renal Physiol 2002, 282:F191–F201.

    PubMed  Google Scholar 

  20. Seaberg EC, Munoz A, Lu M, et al.: Association between highly active antiretroviral therapy and hypertension in a large cohort of men followed from 1984 to 2003. AIDS 2005, 19:953–960.

    Article  PubMed  Google Scholar 

  21. Rodriguez-Iturbe B, Vaziri ND, Herrera-Acosta J, et al.: Oxidative stress, renal infiltration of immune cells, and salt-sensitive hypertension: all for one and one for all. Am J Physiol Renal Physiol 2004, 286:F606–F616.

    Article  PubMed  CAS  Google Scholar 

  22. Fu ML: Do immune system changes have a role in hypertension? J Hypertens 1995, 13:1259–1265.

    Article  PubMed  CAS  Google Scholar 

  23. Dzielak DJ: The immune system and hypertension. Hypertension 1992, 19:I36–I44.

    PubMed  CAS  Google Scholar 

  24. Dzielak DJ: Immune mechanisms in experimental and essential hypertension. Am J Physiol 1991, 260:R459–R467.

    PubMed  CAS  Google Scholar 

  25. Kawanishi M: Nitric oxide inhibits Epstein-Barr virus DNA replication and activation of latent EBV. Intervirology 1995, 38:206–213.

    PubMed  CAS  Google Scholar 

  26. Jimenez R, Belcher E, Sriskandan S, et al.: Role of Toll-like receptors 2 and 4 in the induction of cyclooxygenase-2 in vascular smooth muscle. Proc Natl Acad Sci U S A 2005, 102:4637–4642.

    Article  PubMed  CAS  Google Scholar 

  27. Miller YI, Chang MK, Binder CJ, et al.: Oxidized low density lipoprotein and innate immune receptors. Curr Opin Lipidol 2003, 14:437–445.

    Article  PubMed  CAS  Google Scholar 

  28. Abbas A, Lichtman A, eds: Cellular and Molecular Immunology, edn 5. Philadelphia, PA: Elsevier Saunders; 2005.

    Google Scholar 

  29. Shimada K, Yazaki Y: Binding sites for angiotensin II in human mononuclear leucocytes. J Biochem 1978, 84:1013–1015.

    PubMed  CAS  Google Scholar 

  30. Nataraj C, Oliverio MI, Mannon RB, et al.: Angiotensin II regulates cellular immune responses through a calcineurin-dependent pathway. J Clin Invest 1999, 104:1693–1701.

    Google Scholar 

  31. Amuchastegui SC, Azzollini N, Mister M, et al.: Chronic allograft nephropathy in the rat is improved by angiotensin II receptor blockade but not by calcium channel antagonism. J Am Soc Nephrol 1998, 9:1948–1955.

    PubMed  CAS  Google Scholar 

  32. Furukawa Y, Matsumori A, Hirozane T, et al.: Angiotensin II receptor antagonist TCV-116 reduces graft coronary artery disease and preserves graft status in a murine model. A comparative study with captopril. Circulation 1996, 93:333–339.

    PubMed  CAS  Google Scholar 

  33. Booster MH, Yin M, Maessen JG, et al.: Protection of canine renal grafts by renin-angiotensin inhibition through nucleoside transport blockade. Transpl Int 1995, 8:207–213.

    Article  PubMed  CAS  Google Scholar 

  34. Otsuka F, Yamauchi T, Kataoka H, et al.: Effects of chronic inhibition of ACE and AT1 receptors on glomerular injury in Dahl salt-sensitive rats. Am J Physiol 1998, 274:R1797–R1806.

    PubMed  CAS  Google Scholar 

  35. Velasquez MT, Striffler JS, Abraham AA, et al.: Perindopril ameliorates glomerular and renal tubulointerstitial injury in the SHR/N-corpulent rat. Hypertension 1997, 30:1232–1237.

    PubMed  CAS  Google Scholar 

  36. Shibouta Y, Chatani F, Ishimura Y, et al.: TCV-116 inhibits renal interstitial and glomerular injury in glomerulosclerotic rats. Kidney Int Suppl 1996, 55:S115–S118.

    PubMed  CAS  Google Scholar 

  37. Shao J, Nangaku M, Miyata T, et al.: Imbalance of T-cell subsets in angiotensin II-infused hypertensive rats with kidney injury. Hypertension 2003, 42:31–38.

    Article  PubMed  CAS  Google Scholar 

  38. Fernandez-Castelo S, Arzt ES, Pesce A, et al.: Angiotensin II regulates interferon-gamma production. J Interferon Res 1987, 7:261–268.

    PubMed  CAS  Google Scholar 

  39. Diet F, Pratt RE, Berry GJ, et al.: Increased accumulation of tissue ACE in human atherosclerotic coronary artery disease. Circulation 1996, 94:2756–2767.

    PubMed  CAS  Google Scholar 

  40. Potter DD, Sobey CG, Tompkins PK, et al.: Evidence that macrophages in atherosclerotic lesions contain angiotensin II. Circulation 1998, 98:800–807.

    PubMed  CAS  Google Scholar 

  41. Danilov SM, Sadovnikova E, Scharenborg N, et al.: Angiotensin-converting enzyme (CD143) is abundantly expressed by dendritic cells and discriminates human monocyte-derived dendritic cells from acute myeloid leukemia-derived dendritic cells. Exp Hematol 2003, 31:1301–1309.

    Article  PubMed  CAS  Google Scholar 

  42. Guruli G, Pflug BR, Pecher S, et al.: Function and survival of dendritic cells depend on endothelin-1 and endothelin receptor autocrine loops. Blood 2004, 104:2107–2115.

    Article  PubMed  CAS  Google Scholar 

  43. Guzik TJ, Hoch NE, Brown KA, et al.: Role of the T cell in the genesis of angiotensin II induced hypertension and vascular dysfunction. J Exp Med 2007, 204:2449–2460.

    Article  PubMed  CAS  Google Scholar 

  44. Elmarakby AA, Quigley JE, Pollock DM, et al.: Tumor necrosis factor alpha blockade increases renal Cyp2c23 expression and slows the progression of renal damage in salt-sensitive hypertension. Hypertension 2006, 47:557–562.

    Article  PubMed  CAS  Google Scholar 

  45. Jonasson L, Holm J, Skalli O, et al.: Regional accumulations of T cells, macrophages, and smooth muscle cells in the human atherosclerotic plaque. Arteriosclerosis 1986, 6:131–138.

    PubMed  CAS  Google Scholar 

  46. Jonasson L, Holm J, Skalli O, et al.: Expression of class II transplantation antigen on vascular smooth muscle cells in human atherosclerosis. J Clin Invest 1985, 76:125–131.

    Article  PubMed  CAS  Google Scholar 

  47. Agrewala JN, Brown DM, Lepak NM, et al.: Unique ability of activated CD4+ T cells but not rested effectors to migrate to non-lymphoid sites in the absence of inflammation. J Biol Chem 2007, 282:6106–6115.

    Article  PubMed  CAS  Google Scholar 

  48. Wu H, Ghosh S, Perrard XD, et al.: T-cell accumulation and regulated on activation, normal T cell expressed and secreted upregulation in adipose tissue in obesity. Circulation 2007, 115:1029–1038.

    Article  PubMed  CAS  Google Scholar 

  49. Angeli F, Verdecchia P, Pellegrino C, et al.: Association between periodontal disease and left ventricle mass in essential hypertension. Hypertension 2003, 41:488–492.

    Article  PubMed  CAS  Google Scholar 

  50. Vlachopoulos C, Dima I, Aznaouridis K, et al.: Acute systemic inflammation increases arterial stiffness and decreases wave reflections in healthy individuals. Circulation 2005, 112:2193–2200.

    Article  PubMed  Google Scholar 

  51. Clapp BR, Hingorani AD, Kharbanda RK, et al.: Inflammation-induced endothelial dysfunction involves reduced nitric oxide bioavailability and increased oxidant stress. Cardiovasc Res 2004, 64:172–178.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, Division of Cardiology, Emory University School of Medicine, Room 319 WMRB, 1639 Pierce Drive, Atlanta, GA, 30322, USA

    David G. Harrison

Authors
  1. David G. Harrison
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tomasz J. Guzik
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jorg Goronzy
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Cornelia Weyand
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David G. Harrison.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Harrison, D.G., Guzik, T.J., Goronzy, J. et al. Is hypertension an immunologic disease?. Curr Cardiol Rep 10, 464–469 (2008). https://doi.org/10.1007/s11886-008-0073-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11886-008-0073-6

Keywords

Search

Navigation