Current Hypertension Reports

, 20:100 | Cite as

Inflammation as a Regulator of the Renin-Angiotensin System and Blood Pressure

  • Ryousuke SatouEmail author
  • Harrison Penrose
  • L. Gabriel Navar
Mechanisms of Hypertension (M Weir, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Mechanisms of Hypertension


Purpose of Review

Mechanisms facilitating progression of hypertension via cross stimulation of the renin-angiotensin system (RAS) and inflammation have been proposed. Accordingly, we review and update evidence for regulation of RAS components by pro-inflammatory factors.

Recent Findings

Angiotensin II (Ang II), which is produced by RAS, induces vasoconstriction and consequent blood pressure elevation. In addition to this direct action, chronically elevated Ang II stimulates several pathophysiological mechanisms including generation of oxidative stress, stimulation of the nervous system, alterations in renal hemodynamics, and activation of the immune system. In particular, an activated immune system has been shown to contribute to the development of hypertension. Recent studies have demonstrated that immune cell-derived pro-inflammatory cytokines regulate RAS components, further accelerating systemic and local Ang II formation. Specifically, regulation of angiotensinogen (AGT) production by pro-inflammatory cytokines in the liver and kidney is proposed as a key mechanism underlying the progression of Ang II-dependent hypertension.


The renin-angiotensin system Inflammation Hypertension Intracellular signaling 


Compliance with Ethical Standards

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.


Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. 1.
    Zhuo JL, Ferrao FM, Zheng Y, Li XC. New frontiers in the intrarenal renin-angiotensin system: a critical review of classical and new paradigms. Front Endocrinol. 2013;4:166. Scholar
  2. 2.
    Navar LG, Prieto MC, Satou R, Kobori H. Intrarenal angiotensin II and its contribution to the genesis of chronic hypertension. Curr Opin Pharmacol. 2011;11(2):180–6. Scholar
  3. 3.
    Rudemiller NP, Crowley SD. Interactions between the immune and the renin-angiotensin systems in hypertension. Hypertension. 2016;68(2):289–96. Scholar
  4. 4.
    Nataraj C, Oliverio MI, Mannon RB, Mannon PJ, Audoly LP, Amuchastegui CS, et al. Angiotensin II regulates cellular immune responses through a calcineurin-dependent pathway. J Clin Invest. 1999;104(12):1693–701. Scholar
  5. 5.
    Suzuki Y, Ruiz-Ortega M, Gomez-Guerrero C, Tomino Y, Egido J. Angiotensin II, the immune system and renal diseases: another road for RAS? Nephrol Dial Transplant. 2003;18(8):1423–6.CrossRefGoogle Scholar
  6. 6.
    Harrison DG, Guzik TJ, Lob HE, Madhur MS, Marvar PJ, Thabet SR, et al. Inflammation, immunity, and hypertension. Hypertension. 2011;57(2):132–40. Scholar
  7. 7.
    Rodriguez-Iturbe B, Pons H, Johnson RJ. Role of the immune system in hypertension. Physiol Rev. 2017;97(3):1127–64. Scholar
  8. 8.
    Reis F, Parada B, Teixeira de Lemos E, Garrido P, Dias A, Piloto N, et al. Hypertension induced by immunosuppressive drugs: a comparative analysis between sirolimus and cyclosporine. Transplant Proc. 2009;41(3):868–73. Scholar
  9. 9.
    Divac N, Naumovic R, Stojanovic R, Prostran M. The role of immunosuppressive medications in the pathogenesis of hypertension and efficacy and safety of antihypertensive agents in kidney transplant recipients. Curr Med Chem. 2016;23(19):1941–52.CrossRefGoogle Scholar
  10. 10.
    Bravo Y, Quiroz Y, Ferrebuz A, Vaziri ND, Rodriguez-Iturbe B. Mycophenolate mofetil administration reduces renal inflammation, oxidative stress, and arterial pressure in rats with lead-induced hypertension. Am J Physiol Renal Physiol. 2007;293(2):F616–23. Scholar
  11. 11.
    Khraibi AA, Norman RA Jr, Dzielak DJ. Chronic immunosuppression attenuates hypertension in Okamoto spontaneously hypertensive rats. Am J Phys. 1984;247(5 Pt 2):H722–6. Scholar
  12. 12.
    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. Scholar
  13. 13.
    •• 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. This study revealed that elevated expression of CD70 in macrophages and dendritic cells coupled with exhaustion of effector memory T cells are essential mechanisms to sustain high blood pressure. CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    McCarthy CG, Goulopoulou S, Wenceslau CF, Spitler K, Matsumoto T, Webb RC. Toll-like receptors and damage-associated molecular patterns: novel links between inflammation and hypertension. Am J Physiol Heart Circ Physiol. 2014;306(2):H184–96. Scholar
  15. 15.
    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. Scholar
  16. 16.
    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. Scholar
  17. 17.
    Rickard AJ, Morgan J, Tesch G, Funder JW, Fuller PJ, Young MJ. Deletion of mineralocorticoid receptors from macrophages protects against deoxycorticosterone/salt-induced cardiac fibrosis and increased blood pressure. Hypertension. 2009;54(3):537–43. Scholar
  18. 18.
    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. Scholar
  19. 19.
    •• Justin Rucker A, Crowley SD. The role of macrophages in hypertension and its complications. Pflugers Arch. 2017;469(3-4):419–30. The authors reviewed important roles of macrophages in the development of hypertension. CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Hahn AW, Jonas U, Buhler FR, Resink TJ. Activation of human peripheral monocytes by angiotensin II. FEBS Lett. 1994;347(2–3):178–80.CrossRefGoogle Scholar
  21. 21.
    Suzuki Y, Ruiz-Ortega M, Lorenzo O, Ruperez M, Esteban V, Egido J. Inflammation and angiotensin II. Int J Biochem Cell Biol. 2003;35(6):881–900.CrossRefGoogle Scholar
  22. 22.
    Piqueras L, Kubes P, Alvarez A, O'Connor E, Issekutz AC, Esplugues JV, et al. Angiotensin II induces leukocyte-endothelial cell interactions in vivo via AT(1) and AT(2) receptor-mediated P-selectin upregulation. Circulation. 2000;102(17):2118–23.CrossRefGoogle Scholar
  23. 23.
    Ma LJ, Corsa BA, Zhou J, Yang H, Li H, Tang YW, et al. Angiotensin type 1 receptor modulates macrophage polarization and renal injury in obesity. Am J Physiol Renal Physiol. 2011;300(5):F1203–13. Scholar
  24. 24.
    Nishida M, Fujinaka H, Matsusaka T, Price J, Kon V, Fogo AB, et al. Absence of angiotensin II type 1 receptor in bone marrow-derived cells is detrimental in the evolution of renal fibrosis. J Clin Invest. 2002;110(12):1859–68. Scholar
  25. 25.
    Zhang JD, Patel MB, Griffiths R, Dolber PC, Ruiz P, Sparks MA, et al. Type 1 angiotensin receptors on macrophages ameliorate IL-1 receptor-mediated kidney fibrosis. J Clin Invest. 2014;124(5):2198–203. Scholar
  26. 26.
    Zhang L, Du J, Hu Z, Han G, Delafontaine P, Garcia G, et al. IL-6 and serum amyloid a synergy mediates angiotensin II-induced muscle wasting. J Am Soc Nephrol. 2009;20(3):604–12. Scholar
  27. 27.
    Recinos A 3rd, LeJeune WS, Sun H, Lee CY, Tieu BC, Lu M, et al. Angiotensin II induces IL-6 expression and the Jak-STAT3 pathway in aortic adventitia of LDL receptor-deficient mice. Atherosclerosis. 2007;194(1):125–33. Scholar
  28. 28.
    Wei Z, Spizzo I, Diep H, Drummond GR, Widdop RE, Vinh A. Differential phenotypes of tissue-infiltrating T cells during angiotensin II-induced hypertension in mice. PLoS One. 2014;9(12):e114895. Scholar
  29. 29.
    Qi G, Jia L, Li Y, Bian Y, Cheng J, Li H, et al. Angiotensin II infusion-induced inflammation, monocytic fibroblast precursor infiltration, and cardiac fibrosis are pressure dependent. Cardiovasc Toxicol. 2011;11(2):157–67. Scholar
  30. 30.
    Ozawa Y, Kobori H, Suzaki Y, Navar LG. Sustained renal interstitial macrophage infiltration following chronic angiotensin II infusions. Am J Physiol Renal Physiol. 2007;292(1):F330–9. Scholar
  31. 31.
    Ruiz-Ortega M, Ruperez M, Lorenzo O, Esteban V, Blanco J, Mezzano S, et al. Angiotensin II regulates the synthesis of proinflammatory cytokines and chemokines in the kidney. Kidney Int Suppl. 2002;62(82):12–22. Scholar
  32. 32.
    Meng Y, Chen C, Liu Y, Tian C, Li HH. Angiotensin II regulates dendritic cells through activation of NF-kappaB /p65, ERK1/2 and STAT1 pathways. Cell Physiol Biochem. 2017;42(4):1550–8. Scholar
  33. 33.
    Iwashita M, Sakoda H, Kushiyama A, Fujishiro M, Ohno H, Nakatsu Y, et al. Valsartan, independently of AT1 receptor or PPARgamma, suppresses LPS-induced macrophage activation and improves insulin resistance in cocultured adipocytes. Am J Physiol Endocrinol Metab. 2012;302(3):E286–96. Scholar
  34. 34.
    Guo F, Chen XL, Wang F, Liang X, Sun YX, Wang YJ. Role of angiotensin II type 1 receptor in angiotensin II-induced cytokine production in macrophages. J Interf Cytokine Res. 2011;31(4):351–61. Scholar
  35. 35.
    •• O'Leary R, Penrose H, Miyata K, Satou R. Macrophage-derived IL-6 contributes to ANG II-mediated angiotensinogen stimulation in renal proximal tubular cells. Am J Physiol Renal Physiol. 2016;310(10):F1000–7. This study demonstrated that elevated IL-6 derived from Ang II-treated macrophages stimulates AGT expression in PTC. CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Ferrario CM. ACE2: more of Ang-(1-7) or less Ang II? Curr Opin Nephrol Hypertens. 2011;20(1):1–6. Scholar
  37. 37.
    Simoes e Silva AC, Silveira KD, Ferreira AJ, Teixeira MM. ACE2, angiotensin-(1-7) and Mas receptor axis in inflammation and fibrosis. Br J Pharmacol. 2013;169(3):477–92. Scholar
  38. 38.
    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. Scholar
  39. 39.
    Dzau VJ, Re R. Tissue angiotensin system in cardiovascular medicine. A paradigm shift? Circulation. 1994;89(1):493–8.CrossRefGoogle Scholar
  40. 40.
    Tamura K, Tanimoto K, Takahashi S, Sagara M, Fukamizu A, Murakami K. Structure and expression of the mouse angiotensinogen gene. Jpn Heart J. 1992;33(1):113–24.CrossRefGoogle Scholar
  41. 41.
    Paul M, Poyan Mehr A, Kreutz R. Physiology of local renin-angiotensin systems. Physiol Rev. 2006;86(3):747–803. Scholar
  42. 42.
    Re RN. Tissue renin angiotensin systems. Med Clin North Am. 2004;88(1):19–38.CrossRefGoogle Scholar
  43. 43.
    Corvol P, Jeunemaitre X. Molecular genetics of human hypertension: role of angiotensinogen. Endocr Rev. 1997;18(5):662–77. Scholar
  44. 44.
    Kim HS, Krege JH, Kluckman KD, Hagaman JR, Hodgin JB, Best CF, et al. Genetic control of blood pressure and the angiotensinogen locus. Proc Natl Acad Sci U S A. 1995;92(7):2735–9.CrossRefGoogle Scholar
  45. 45.
    Jain S, Li Y, Patil S, Kumar A. HNF-1alpha plays an important role in IL-6-induced expression of the human angiotensinogen gene. Am J Physiol Cell Physiol. 2007;293(1):C401–10. Scholar
  46. 46.
    htani R, Yayama K, Takano M, Itoh N, Okamoto H. Stimulation of angiotensinogen production in primary cultures of rat hepatocytes by glucocorticoid, cyclic adenosine 3′,5′-monophosphate, and interleukin-6. Endocrinology. 1992;130(3):1331–8. Scholar
  47. 47.
    Ray S, Boldogh I, Brasier AR. STAT3 NH2-terminal acetylation is activated by the hepatic acute-phase response and required for IL-6 induction of angiotensinogen. Gastroenterology. 2005;129(5):1616–32. Scholar
  48. 48.
    Brasier AR, Recinos A 3rd, Eledrisi MS. Vascular inflammation and the renin-angiotensin system. Arterioscler Thromb Vasc Biol. 2002;22(8):1257–66.CrossRefGoogle Scholar
  49. 49.
    Brasier AR, Ron D, Tate JE, Habener JF. A family of constitutive C/EBP-like DNA binding proteins attenuate the IL-1 alpha induced, NF kappa B mediated trans-activation of the angiotensinogen gene acute-phase response element. EMBO J. 1990;9(12):3933–44.CrossRefGoogle Scholar
  50. 50.
    Sherman CT, Brasier AR. Role of signal transducers and activators of transcription 1 and −3 in inducible regulation of the human angiotensinogen gene by interleukin-6. Mol Endocrinol. 2001;15(3):441–57. Scholar
  51. 51.
    Jain S, Shah M, Li Y, Vinukonda G, Sehgal PB, Kumar A. Upregulation of human angiotensinogen (AGT) gene transcription by interferon-gamma: involvement of the STAT1-binding motif in the AGT promoter. Biochim Biophys Acta. 2006;1759(7):340–7. Scholar
  52. 52.
    Kobori H, Harrison-Bernard LM, Navar LG. Expression of angiotensinogen mRNA and protein in angiotensin II-dependent hypertension. J Am Soc Nephrol. 2001;12(3):431–9.PubMedPubMedCentralGoogle Scholar
  53. 53.
    Gonzalez-Villalobos RA, Seth DM, Satou R, Horton H, Ohashi N, Miyata K, et al. Intrarenal angiotensin II and angiotensinogen augmentation in chronic angiotensin II-infused mice. Am J Physiol Renal Physiol. 2008;295(3):F772–9. Scholar
  54. 54.
    Kobori H, Ozawa Y, Satou R, Katsurada A, Miyata K, Ohashi N, et al. Kidney-specific enhancement of ANG II stimulates endogenous intrarenal angiotensinogen in gene-targeted mice. Am J Physiol Renal Physiol. 2007;293(3):F938–45. Scholar
  55. 55.
    Ingelfinger JR, Jung F, Diamant D, Haveran L, Lee E, Brem A, et al. Rat proximal tubule cell line transformed with origin-defective SV40 DNA: autocrine ANG II feedback. Am J Phys. 1999;276(2 Pt 2):F218–27.Google Scholar
  56. 56.
    Satou R, Gonzalez-Villalobos RA, Miyata K, Ohashi N, Katsurada A, Navar LG, et al. Costimulation with angiotensin II and interleukin 6 augments angiotensinogen expression in cultured human renal proximal tubular cells. Am J Physiol Renal Physiol. 2008;295(1):F283–9. Scholar
  57. 57.
    Urushihara M, Ohashi N, Miyata K, Satou R, Acres OW, Kobori H. Addition of angiotensin II type 1 receptor blocker to CCR2 antagonist markedly attenuates crescentic glomerulonephritis. Hypertension. 2011;57(3):586–93. Scholar
  58. 58.
    Lee DL, Sturgis LC, Labazi H, Osborne JB Jr, Fleming C, Pollock JS, et al. Angiotensin II hypertension is attenuated in interleukin-6 knockout mice. Am J Physiol Heart Circ Physiol. 2006;290(3):H935–40. Scholar
  59. 59.
    Banes-Berceli AK, Al-Azawi H, Proctor D, Qu H, Femminineo D, Hill-Pyror C, et al. Angiotensin II utilizes Janus kinase 2 in hypertension, but not in the physiological control of blood pressure, during low-salt intake. Am J Physiol Regul Integr Comp Physiol. 2011;301(4):R1169–76. Scholar
  60. 60.
    Satou R, Miyata K, Gonzalez-Villalobos RA, Ingelfinger JR, Navar LG, Kobori H. Interferon-gamma biphasically regulates angiotensinogen expression via a JAK-STAT pathway and suppressor of cytokine signaling 1 (SOCS1) in renal proximal tubular cells. FASEB J. 2012;26(5):1821–30. Scholar
  61. 61.
    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. Scholar
  62. 62.
    Sriramula S, Francis J. Tumor necrosis factor - alpha is essential for angiotensin II-induced ventricular remodeling: role for oxidative stress. PLoS One. 2015;10(9):e0138372. Scholar
  63. 63.
    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. Scholar
  64. 64.
    Flesch M, Hoper A, Dell'Italia L, Evans K, Bond R, Peshock R, et al. Activation and functional significance of the renin-angiotensin system in mice with cardiac restricted overexpression of tumor necrosis factor. Circulation. 2003;108(5):598–604. Scholar
  65. 65.
    Wang B, Jenkins JR, Trayhurn P. Expression and secretion of inflammation-related adipokines by human adipocytes differentiated in culture: integrated response to TNF-alpha. Am J Physiol Endocrinol Metab. 2005;288(4):E731–40.CrossRefGoogle Scholar
  66. 66.
    Guan H, Hou S, Ricciardi RP. DNA binding of repressor nuclear factor-kappaB p50/p50 depends on phosphorylation of Ser337 by the protein kinase a catalytic subunit. J Biol Chem. 2005;280(11):9957–62. Scholar
  67. 67.
    Tong X, Yin L, Washington R, Rosenberg DW, Giardina C. The p50-p50 NF-kappaB complex as a stimulus-specific repressor of gene activation. Mol Cell Biochem. 2004;265(1–2):171–83.CrossRefGoogle Scholar
  68. 68.
    Satou R, Miyata K, Katsurada A, Navar LG, Kobori H. Tumor necrosis factor-{alpha} suppresses angiotensinogen expression through formation of a p50/p50 homodimer in human renal proximal tubular cells. Am J Physiol Cell Physiol. 2010;299(4):C750–9. Scholar
  69. 69.
    Pan L, Wang Y, Jones CA, Glenn ST, Baumann H, Gross KW. Enhancer-dependent inhibition of mouse renin transcription by inflammatory cytokines. Am J Physiol Renal Physiol. 2005;288(1):F117–24. Scholar
  70. 70.
    Liu X, Shi Q, Sigmund CD. Interleukin-1beta attenuates renin gene expression via a mitogen-activated protein kinase kinase-extracellular signal-regulated kinase and signal transducer and activator of transcription 3-dependent mechanism in As4.1 cells. Endocrinology. 2006;147(12):6011–8. Scholar
  71. 71.
    Baumann H, Wang Y, Richards CD, Jones CA, Black TA, Gross KW. Endotoxin-induced renal inflammatory response. Oncostatin M as a major mediator of suppressed renin expression. J Biol Chem. 2000;275(29):22014–9. Scholar
  72. 72.
    Todorov VT, Volkl S, Muller M, Bohla A, Klar J, Kunz-Schughart LA, et al. Tumor necrosis factor-alpha activates NFkappaB to inhibit renin transcription by targeting cAMP-responsive element. J Biol Chem. 2004;279(2):1458–67. Scholar
  73. 73.
    Todorov VT, Volkl S, Friedrich J, Kunz-Schughart LA, Hehlgans T, Vermeulen L, et al. Role of CREB1 and NF{kappa}B-p65 in the down-regulation of renin gene expression by tumor necrosis factor {alpha}. J Biol Chem. 2005;280(26):24356–62. Scholar
  74. 74.
    Ortiz RM, Mamalis A, Navar LG. Aldosterone receptor antagonism reduces urinary C-reactive protein excretion in angiotensin II-infused, hypertensive rats. J Am Soc Hypertens. 2009;3(3):184–91. Scholar
  75. 75.
    Navar LG, Kobori H, Prieto MC, Gonzalez-Villalobos RA. Intratubular renin-angiotensin system in hypertension. Hypertension. 2011;57(3):355–62. Scholar
  76. 76.
    Prieto MC, Williams DE, Liu L, Kavanagh KL, Mullins JJ, Mitchell KD. Enhancement of renin and prorenin receptor in collecting duct of Cyp1a1-Ren2 rats may contribute to development and progression of malignant hypertension. Am J Physiol Renal Physiol. 2011;300(2):F581–8. Scholar
  77. 77.
    Prieto MC, Reverte V, Mamenko M, Kuczeriszka M, Veiras LC, Rosales CB, et al. Collecting duct prorenin receptor knockout reduces renal function, increases sodium excretion, and mitigates renal responses in ANG II-induced hypertensive mice. Am J Physiol Renal Physiol. 2017;313(6):F1243–F53. Scholar
  78. 78.
    Hanafy S, Tavasoli M, Jamali F. Inflammation alters angiotensin converting enzymes (ACE and ACE-2) balance in rat heart. Inflammation. 2011;34(6):609–13. Scholar
  79. 79.
    Sakuta T, Morita Y, Satoh M, Fox DA, Kashihara N. Involvement of the renin-angiotensin system in the development of vascular damage in a rat model of arthritis: effect of angiotensin receptor blockers. Arthritis Rheum. 2010;62(5):1319–28. Scholar
  80. 80.
    Sekiguchi K, Li X, Coker M, Flesch M, Barger PM, Sivasubramanian N, et al. Cross-regulation between the renin-angiotensin system and inflammatory mediators in cardiac hypertrophy and failure. Cardiovasc Res. 2004;63(3):433–42. Scholar
  81. 81.
    Wei SG, Yu Y, Zhang ZH, Felder RB. Proinflammatory cytokines upregulate sympathoexcitatory mechanisms in the subfornical organ of the rat. Hypertension. 2015;65(5):1126–33. Scholar
  82. 82.
    Garcia V, Shkolnik B, Milhau L, Falck JR, Schwartzman ML. 20-HETE activates the transcription of angiotensin-converting enzyme via nuclear factor-kappaB translocation and promoter binding. J Pharmacol Exp Ther. 2016;356(3):525–33. Scholar
  83. 83.
    Kobori H, Nangaku M, Navar LG, Nishiyama A. The intrarenal renin-angiotensin system: from physiology to the pathobiology of hypertension and kidney disease. Pharmacol Rev. 2007;59(3):251–87. Scholar
  84. 84.
    Gutkind JS, Kurihara M, Castren E, Saavedra JM. Increased concentration of angiotensin II binding sites in selected brain areas of spontaneously hypertensive rats. J Hypertens. 1988;6(1):79–84.CrossRefGoogle Scholar
  85. 85.
    Hu L, Zhu DN, Yu Z, Wang JQ, Sun ZJ, Yao T. Expression of angiotensin II type 1 (AT(1)) receptor in the rostral ventrolateral medulla in rats. J Appl Physiol. 2002;92(5):2153–61. Scholar
  86. 86.
    Cheng HF, Becker BN, Burns KD, Harris RC. Angiotensin II upregulates type-1 angiotensin II receptors in renal proximal tubule. J Clin Invest. 1995;95(5):2012–9. Scholar
  87. 87.
    Yoshida T, Galvez S, Tiwari S, Rezk BM, Semprun-Prieto L, Higashi Y, et al. Angiotensin II inhibits satellite cell proliferation and prevents skeletal muscle regeneration. J Biol Chem. 2013;288(33):23823–32. Scholar
  88. 88.
    Coles B, Fielding CA, Rose-John S, Scheller J, Jones SA, O'Donnell VB. Classic interleukin-6 receptor signaling and interleukin-6 trans-signaling differentially control angiotensin II-dependent hypertension, cardiac signal transducer and activator of transcription-3 activation, and vascular hypertrophy in vivo. Am J Pathol. 2007;171(1):315–25. Scholar
  89. 89.
    Herrera M, Sparks MA, Alfonso-Pecchio AR, Harrison-Bernard LM, Coffman TM. Lack of specificity of commercial antibodies leads to misidentification of angiotensin type 1 receptor protein. Hypertension. 2013;61(1):253–8. Scholar
  90. 90.
    Iwai N, Inagami T, Ohmichi N, Nakamura Y, Saeki Y, Kinoshita M. Differential regulation of rat AT1a and AT1b receptor mRNA. Biochem Biophys Res Commun. 1992;188(1):298–303.CrossRefGoogle Scholar
  91. 91.
    Dinh QN, Drummond GR, Kemp-Harper BK, Diep H, De Silva TM, Kim HA, et al. Pressor response to angiotensin II is enhanced in aged mice and associated with inflammation, vasoconstriction and oxidative stress. Aging. 2017;9(6):1595–606. Scholar
  92. 92.
    Takeda-Matsubara Y, Matsubara K, Ochi H, Ito M, Iwai M, Horiuchi M. Expression of endothelial angiotensin II receptor mRNA in pregnancy-induced hypertension. Am J Hypertens. 2003;16(12):993–9.CrossRefGoogle Scholar
  93. 93.
    Wang H, Jia D, Shen H, Tao Q, Liu L, Zhang L, et al. Effects of cytokines on the expression of angiotensin II type 1 receptors in vascular smooth muscle cells. Int J Clin Exp Med. 2016;9(1):219–25.Google Scholar
  94. 94.
    Wei SG, Yu Y, Zhang ZH, Felder RB. Angiotensin II upregulates hypothalamic AT1 receptor expression in rats via the mitogen-activated protein kinase pathway. Am J Physiol Heart Circ Physiol. 2009;296(5):H1425–33. Scholar
  95. 95.
    Kawakami Y, Matsuo K, Murata M, Yudoh K, Nakamura H, Shimizu H, et al. Expression of angiotensin II receptor-1 in human articular chondrocytes. Arthritis. 2012;2012:648537. Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Ryousuke Satou
    • 1
    Email author
  • Harrison Penrose
    • 1
  • L. Gabriel Navar
    • 1
  1. 1.Department of Physiology and Hypertension and Renal Center of ExcellenceTulane University School of MedicineNew OrleansUSA

Personalised recommendations