Seminars in Nephrology
Volume 24, Issue 2 , Pages 93-100 , March 2004

AT1 and AT2 receptor in the kidney: role in health and disease

  • Helmy M Siragy

      Affiliations

    • Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA
    • Corresponding Author InformationAddress reprint requests to Helmy M. Siragy, MD, FACP, FAHA, Professor of Medicine and Endocrinology, University of Virginia Health System, P.O. Box 801409, Charlottesville, VA 22908 USA

References 

  1. Zitnay C, Siragy HM. Action of angiotensin receptor subtypes on the renal tubules and vasculature. Implications for volume homeostasis and atherosclerosis. Miner Electrolyte Metab. 1998;24:362–370
  2. Dzau VJ, Sasamura H, Hein L. Heterogeneity of angiotensin synthetic pathways and receptor subtypes (Physiological and pharmacological implications). J Hypertens. 1993;11:S13–S18
  3. Hollenberg NK, Fisher ND, Price DA. Pathways for angiotensin II generation in intact human tissue (Evidence from comparative pharmacological interruption of the renin system). Hypertension. 1998;32:387–392
  4. Siragy HM, Howell NL, Ragsdale NV, Carey RM. Renal interstitial fluid angiotensin. Modulation by anesthesia epinephrine, sodium depletion, and renin inhibition. Hypertension. 1995;25:1021–1024
  5. Murphy TJ, Alexander RW, Griendling KK, Runge MS, Bernstein KE. Isolation of a cDNA encoding the vascular type-1 angiotensin II receptor. Nature. 1991;351:233–236
  6. Sasaki K, Yamano Y, Bardhan S, et al.  Cloning and expression of a complementary DNA encoding a bovine adrenal angiotensin II type-1 receptor. Nature. 1991;351:230–233
  7. Chiu AT, Herblin WF, McCall DE, et al.  Identification of angiotensin II receptor subtypes. Biochem Biophys Res Commun. 1989;165:196–203
  8. Zou Y, Komuro I, Yamazaki T, et al.  Cell type-specific angiotensin II-evoked signal transduction pathways (Critical roles of G-beta-gamma subunit, Src family and Ras in cardiac fibroblasts). Circ Res. 1998;82:337–345
  9. Zhou J, Alcorn D, Allen AM, Mendelsohn FAO. High resolution localization of angiotensin II receptors in rat renal medulla. Kidney Int. 1992;42:1372–1380
  10. Zhuo J, Alcorn D, Harris PJ, Mendelsohn FAO. Localization and properties of angiotensin II receptors in rat kidney. Kidney Int. 1993;42:S40–S46
  11. Healy DP, Ye MQ, Troyanovskaya M. Localization of angiotensin II type 1 receptor subtype mRNA in rat kidney. Am J Physiol. 1995;268:F220–F226
  12. Kakinuma Y, Fogo A, Inagami T, Ichikawa I. Intrarenal localization of angiotensin II type 1 receptor mRNA in the rat. Kidney Int. 1993;43:1129–1235
  13. Paxton WG, Runge M, Horaist C, Cohen C, Alexander RW, Bernstein KE. Immunohistochemical localization of rat angiotensin II AT1 receptor. Am J Physiol. 1993;264:F989–F995
  14. Harrison-Bernard LM, Navar LG, Ho MM, Vinson GP, El-Dahr SS. Immunohistochemical localization of Ang II AT1 receptor in adult rat kidney using a monoclonal antibody. Am J Physiol. 1997;273:F170–F177
  15. Schmitz U, Berk BC. Angiotensin II signal transduction (Stimulation of multiple mitogen-activated protein kinase pathways). Trends Endocrinol Metab. 1997;8:261–266
  16. Siragy HM. Angiotensin receptor blockers (How important is selectivity?). Am J Hypertens. 2002;15:1006–1014
  17. Siragy HM. AT1 and AT2 receptor in the kidney (role in disease and treatment). Am J Kidney Dis. 2000;36:54–59
  18. Kambayashi Y, Bardhan S, Takahashi K, et al.  Molecular cloning of a novel angiotensin II receptor isoform involved in phosphotyrosine phosphatase inhibition. J Biol Chem. 1993;268:24543–245436
  19. Nakajima M, Mukoyama M, Pratt RE, Horiuchi M, Dzau VJ. Cloning of cDNA and analysis of the gene for mouse angiotensin II type 2 receptor. Biochem Biophys Res Commun. 1993;197:393–399
  20. Ozono R, Wang ZQ, Moore AF, Inagami T, Siragy HM, Carey RM. Expression of the subtype 2 angiotensin AT2 receptor protein in rat kidney. Hypertension. 1997;30:1238–1246
  21. Herblin WF, Diamond SM, Timmermans PB. Localization of angiotensin II receptor subtypes in the rabbit adrenal and kidney. Peptides. 1991;12:581–584
  22. Gibson RE, Thorpe HH, Cartwright ME, et al.  Angiotensin II receptor subtypes in renal cortex of rats and rhesus monkeys. Am J Physiol. 1991;261:F512–F518
  23. Arima S, Endo Y, Yaoita H, et al.  Possible role to P-450 metabolite of arachidonic acid in vasodilator mechanism of angiotensin II type 2 receptor in the isolated microperfused rabbit afferent arteriole. J Clin Invest. 1997;100:2816–2823
  24. Kang J, Posner P, Sumners C. Angiotensin II type 2 receptor stimulation of neuronal K+ currents involves an inhibitory GTP binding protein. Am J Physiol Cell Physiol. 1994;36:C1389–C1397
  25. Hayashida W, Horiuchi M, Dzau VJ. Intracellular third loop domain of angiotensin II type-2 receptor—Role in mediating signal transduction and cellular function. J Biol Chem. 1996;271:21985–21992
  26. Zhang JS, Pratt RE. The AT2 receptor selectively associates with G (I-α-2) and g (I-α-3) in the rat fetus. J Biol Chem. 1996;271:15026–15033
  27. Fischer TA, Singh K, Ohara DS, Kaye DM, Kelly RA. Role of AT1 and AT2 receptors in regulation of MAPKS and MKP-1 by Ang II in adult cardiac myocytes. Am J Physiol. 1998;44:H906–H916
  28. Matsubara H, Inada M. Molecular insights into angiotensin II type 1 and type 2 receptors—Expression, signaling and physiological function and clinical application of its antagonists. Endocr J. 1998;45:137–150
  29. Bedecs K, Elbaz N, Sutren M, et al.  Angiotensin II type 2 receptors mediate inhibition of mitogen-activated protein kinase cascade and functional activation of SHP-1 tyrosine phosphatase. Biochem J. 1997;325:449–454
  30. Lehtonen JYA, Horiuchi M, Daviet L, Akishita M, Dzau VJ. Activation of the de novo biosynthesis of sphingolipids mediates angiotensin II type 2 receptor-induced apoptosis. J Biol Chem. 1999;274:16901–16906
  31. Gallinat S, Busche S, Schutze S, Kronke M, Unger T. AT2 receptor stimulation induces generation of ceramides in PC12W cells. FEBS Lett. 1999;443:75–79
  32. Siragy HM, Carey RM. The subtype-2 (AT2) angiotensin receptor regulates renal cycle guanosine 3′, 5′ -monophosphate and AT1 receptor-mediated prostaglandin E2 production in conscious rats. J Clin Invest. 1996;97:1978–1982
  33. Siragy HM, Carey RM. The subtype 2 (AT2) angiotensin receptor mediates renal production of nitric oxide in conscious rats. J Clin Invest. 1997;100:264–269
  34. Siragy HM, de Gasparo M, Carey RM. Angiotensin type 2 receptor mediates valsartan-induced hypotension in conscious rats. Hypertension. 2000;35:1074–1077
  35. Dulin NO, Alexander LD, Harwalkar S, Falck JR, Douglas JG. Phospholipase A2-mediated activation of mitogen-activated protein kinase by angiotensin II. Proc Natl Acad Sci U S A. 1998;95:8098–8102
  36. Jiao H, Cui XL, Torti M, et al.  Arachidonic acid mediates angiotensin II effects on p21ras in renal proximal tubular cells via the tyrosine kinase-Sch-Grb2-Sos pathway. Proc Natl Acad Sci U S A. 1998;95:7417–7421
  37. Zhu MY, Gelband CH, Moore JM, Posner P, Sumners C. Angiotensin II type 2 receptor stimulation of neuronal delayed-rectifier potassium current involves phospholipase A (2) and arachidonic acid. J Neurosci. 1998;18:679–686
  38. Ciuffo GM, Viswanathan M, Seltzer AM, Tsutsumi K, Saavedra JM. Glomerular angiotensin II receptor subtypes during development of rat kidney. Am J Physiol Renal Physiol. 1993;265:F264–F271
  39. Shanmugam S, Corvol P, Gasc JM. Ontogeny of the two angiotensin II type 1 receptor subtypes in rats. Am J Physiol Endocrinol Metab. 1994;267:E828–E836
  40. Kakuchi J, Ichiki T, Kiyama S, et al.  Development expression of renal angiotensin II receptor genes in the mouse. Kidney Int. 1995;47:140–147
  41. Schutz S, Le Moullec JM, Corvol P, Gasc JM. Early expression of all the components of the rennin-angiotensin system in human development. Am J Pathol. 1996;149:2067–2079
  42. Butkus A, Albiston A, Alcorn D, et al.  Ontogeny of angiotensin II receptors, types 1 and 2, in ovine mesonephros and metanephros. Kidney Int. 1997;52:628–636
  43. Miyazaki Y, Tsuchida S, Nishimura H, et al.  Angiotensin induces the urinary peristaltic machinery during the perinatal period. J Clin Invest. 1998;102:1489–1497
  44. Oliverio MI, Kim HS, Ito M, et al.  Reduced growth, abnormal kidney structure, and type 2 (AT2) angiotensin receptor-mediated blood pressure regulation in mice lacking both AT1A and AT1B receptors for angiotensin II. Proc Natl Acad Sci U S A. 1998;95:15496–15501
  45. Tsuchida S, Matsusaka T, Chen X, et al.  Murine double null zygotes of the angiotensin type 1A and 1A receptor genes duplicate severe abnormal phenotypes of angiotensinogen null zygotes. J Clin Invest. 1998;101:755–760
  46. Hashimoto K, Imai K, Yoshimura S, Ohtaki T. Twelve month studies on the chronic toxicity of captopril in rats. J Toxicol Sci. 1981;2:215–246
  47. Ichiki T, Labosky PA, Shiota C, et al.  Effects on blood pressure and exploratory behaviour of mice lacking angiotensin II type-2 receptor. Nature. 1995;377:745–750
  48. Oliverio MI, Best CF, Kim HS, Arendshorst WJ, Smithies O, Coffman TM. Angiotensin II responses in AT1A receptor-deficient mice (a role for AT1B receptors in blood pressure regulation). Am J Physiol Renal Physiol. 1997;272:F515–F520
  49. Friberg P, Sundelin B, Bohman SO, et al.  Rennin-angiotensin system in neonatal rats (Induction of a renal abnormality in response to ACE inhibition or angiotensin II antagonism). Kidney Int. 1994;45:485–492
  50. Tufro-McReddie A, Romano LM, Harris JM, Ferder L, Gomez RA. Angiotensin II regulates nephrogenesis and renal vascular development. Am J Physiol. 1995;269:F110–F115
  51. Spence SG, Allen HL, Cukierski MA, Manson JM, Robertson RT, Eydelloth RS. Defining the susceptible period of developmental toxicity for the AT1-selective angiotensin II receptor antagonist losartan in rats. Teratology. 1995;51:367–382
  52. Naftilan AJ, Oparil S. Inhibition of rennin release from rat kidney slices by the angiotensins. Am J Physiol. 1978;235:F62–F68
  53. Lorenz JN, Weihprecht H, He X, Skott O, Briggs JP, Schnermann J. Effect of adenosine and angiotensin on macula densa-stimulated rennin secretion. Am J Physiol. 1993;265:F187–F194
  54. Tufro-McReddie A, Johns DW, Geary KM, et al.  Angiotensin II type 1 receptor (Role in renal growth and gene expression during normal development). Am J Physiol. 1994;266:F911–F918
  55. Berry C, Touyz R, Dominiczak AF, Webb RC, Johns DG. Angiotensin receptors (signaling, vascular pathophysiology, and interactions with ceramide). Am J Physiol Heart Circ Physiol. 2001;281:H2337–H2365
  56. Arima S, Kohagura K, Abe M, Ito S. Mechanisms that control glomerular hemodynamics. Clin Exp Nephrol. 2001;5:55–61
  57. Berry C, Hamilton CA, Brosnan MJ, et al.  Investigation into the sources of superoxide in human blood vessels (Angiotensin II increases superoxide production in human internal mammary arteries). Circulation. 2000;101:2206–2212
  58. Muller DN, Dechend R, Mervaala EM, et al.  NF-kappa B inhibition ameliorates angiotensin II induced inflammatory damage in rats. Hypertension. 2000;35:193–201
  59. Vaughn DE, Lazos SA, Tong K. Angiotensin II regulates the expression of plasminogen-activator inhibitor-1 in cultured endothelial cells (A potential link between the rennin-angiotensin system and thrombosis). J Clin Invest. 1995;95:995–1001
  60. Boffa JJ, Tharaux PL, Placier S, Ardaillou R, Dussaule JC, Chatziantoniou C. Angiotensin II activates collagen type I gene in the renal vasculature of transgenic mice during inhibition of nitric oxide synthesis (Evidence for an endothelin-mediated mechanism). Circulation. 1999;100:1901–1908
  61. Siragy HM, Carey RM. Protective role of the angiotensin AT2 receptor in a renal wrap hypertension model. Hypertension. 1999;33:1237–1242
  62. Siragy HM, Inagami T, Ichiki T, Carey RM. Sustained hypersensitivity to angiotensin II and its mechanism in mice lacking the subtype-2 (AT2) angiotensin receptor. Proc Natl Acad Sci U S A. 1999;96:6506–6510
  63. Carey RM, Wang ZQ, Siragy HM. Role of the angiotensin type 2 receptor in the regulation of blood pressure and renal function. Hypertension. 2000;35:155–163
  64. Siragy HM, Senbonmatsu T, Ichiki T, Inagami T, Carey RM. Increased renal vasodilator prostanoids prevent hypertension in mice lacking the angiotensin subtype-2 receptor. J Clin Invest. 1999;104:181–188
  65. Matsubara H. Pathophysiological role of angiotensin II type 2 receptor in cardiovascular and renal diseases. Circ Res. 1998;83:1182–1191
  66. Arima S, Ito S. Angiotensin II type 2 receptors in the kidney; evidence for endothelial-cell-mediated renal vasodilatation. Nephrol Dial Transpl. 2000;15:448–451
  67. Gross V, Schunck WH, Honeck H, et al.  Inhibition of pressure natriuresis in mice lacking the AT2 receptor. Kidney Int. 2000;57:191–202
  68. Haithcock D, Jiao H, Cui XL, Hopfer U, Douglas JG. Renal proximal tubular AT2 receptor (signaling and transport). J Am Soc Nephrol. 1999;11:S69–S74
  69. Siragy HM. The role of the AT2 receptor in hypertension. Am J Hypertens. 2000;13:62S–67S
  70. Loyal F, Dornan ES, McQueen J, Boswell F, Kelly M. Angiotensin II increases proto-oncogene expression and phosphoinositide turnover in vascular smooth muscle cells via the angiotensin II AT1 receptor. J Hypertens. 1992;10:1463–1469
  71. Schmieder R, Veelken R, Schobel H, Dominiak P, Mann J, Luft F. Glomerular hyperfiltration during sympathetic nervous system activation in early essential hypertension. J Am Soc Nephrol. 1997;8:893–900
  72. Kost CK, Herzer W, Li P, et al.  Angiotensin II-induced structural and functional alterations in spontaneously hypertensive rat kidney. Am J Physiol. 1996;270:F229–F236
  73. Brannstrom K, Morsing P, Arendshorst W. Exaggerated tubuloglomerular feedback activity in genetic hypertension is mediated by ANG-II and AT-II. Am J Physiol. 1996;270:F749–F755
  74. Hein L, Barsh GS, Pratt RE, Dzau VJ, Kobilka BK. Behavioural and cardiovascular effects of disrupting the angiotensin II type-2 receptor in mice. Nature. 1995;377:744–747
  75. Bernstein KE, Alexander W. Counterpoint (Molecular analysis of angiotensin II receptor). Endocr Rev. 1992;13:381–386
  76. Phoon S, Howes LG. Forearm vasodilator response to angiotensin II in elderly women receiving candesartan (Role of AT2 receptor). J Renin Angiotensin Aldosterone Syst. 2002;3:36–39
  77. Carey RM, Howell NL, Jin X-H, Siragy HM. Angiotensin type-2 receptor-mediated hypotension in angiotensin type-1 receptor blocked rats. Hypertension. 2001;38:1272–1277
  78. Brenner BM, Cooper ME, de Zeeuw D, et al.  Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes mellitus and nephropathy. N Engl J Med. 2001;345:861–869
  79. Lewis EJ, Hunsicker LG, Clarke WR, et al.  Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001;345:851–860
  80. Parving HH, Lehnert H, Brochner-Mortensen J, Gomis R, Andersen S, Arner P. Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria Study Group (The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes). N Engl J Med. 2001;345:870–878
  81. Thaiss F, Wolf G, Assad N, Zahner G, Stahl RA. Angiotensinase A gene expression and enzyme activity in isolated glomeruli of diabetic rats. Diabetologia. 1996;39:275–280
  82. Kennefick TM, Oyama TT, Thompson MM, Vora JP, Anderson S. Enhanced renal sensitivity to angiotensin actions in diabetes mellitus in the rat. Am J Physiol. 1996;271:595–602
  83. Wolf G. Molecular mechanisms of angiotensin II in the kidney: emerging role in the progression of renal disease: Beyond haemodynamics. Nephrol Dial Transplant. 1998;13:1131–1142
  84. Wolf G, Mueller E, Stahl RAK, Ziyadeh FN. Angiotensin II-induced hypertrophy of cultured murine proximal tubular cells in mediated by endogenous transforming growth factor-β. J Clin Invest. 1993;92:1366–1372
  85. Wolf G, Sharma K, Chen Y, Ericksen M, Ziyadeh FN. High glucose-induced proliferation in mesangial cells is reversed by autocrine TGF-β. Kidney Int. 1992;41:369–402
  86. Ziyadeh FN, Han DC, Cohen J, Guo J, Cohen MP. Glycated albumin stimulates fibronectin gene expression in glomerular mesangial cells (Involvement of the TGF-β system). Kidney Int. 1998;53:631–638
  87. Ziyadeh FN, Sharma K, Ericksen M, Wolf G. Stimulation of collagen gene expression and protein synthesis in murine mesangial cells by high glucose in mediated by activation of transforming growth factor-β. J Clin Invest. 1994;93:536–542
  88. Sharma K, Jin Y, Cuo J, Ziyadeh FN. Neutralization of TGF-β by anti-TGF-β antibody attenuates kidney hypertrophy and the enhanced extracellular matrix gene expression in STZ-induced diabetic mice. Diabetes. 1996;45:522–530
  89. Flyvbjerg A, Orskov H. Kidney tissue insulin-like growth factor I and initial renal growth in diabetic rat (Relation to severity of diabetes). Acta Endocrinol. 1990;122:374–378
  90. Hammerman MR. The growth hormone-insulin-like growth factor axis in kidney. Am J Physiol. 1989;257:503–514
  91. Flyvbjerg A, Bornfeldt KE, Marshall SM, Arnqvist OH. Kidney IGF-I mRNA in initial renal hypertrophy in experimental diabetes in rats. Diabetologia. 1990;33:334–338
  92. Phillip M, Segeve Y, Zung A, et al.  the accumulation of IGF-I in kidneys of streptozotocin-diabetic adult rats is not associated with elevated plasma GH or IGF-I levels. Endocrine. 1995;3:689–693
  93. Flyvbjerg A, Marshall SM, Frystyk J, Hansen KW, Harris AG, Orskov H. Octreotide administration in diabetic rats (Effects on renal hypertrophy and urinary albumin excretion). Kidney Int. 1995;48:45–51
  94. Cooper ME, Vranes D, Youssef S, et al.  Increased renal expression of vascular endothelial growth factor (VEGF) and its receptor VEFR-2 in experimental diabetes. Diabetes. 1999;48:2229–2239
  95. Pupilli C, Lasagni L, Romagnani P, et al.  Angiotensin II stimulates the synthesis and secretion of vascular permeability factor/vascular endothelial growth factor in human mesangial cells. J Am Soc Nephrol. 1999;10:245–255
  96. Siragy HM, Awad AA, Abadir PM, Webb R. The angiotensin II type 1 receptor mediates renal interstitial content of tumor necrosis factor-α in diabetic rats. Endocrinology. 2003;144:2229–2233
  97. Harris RC, Hoover RL, Jacobsen HR, Badr KF. Evidence for glomerular actions of epidermal growth in the rat. J Clin Invest. 1998;82:1028–1039
  98. Vehaskari VM, Hering-Smith KS, Moskowitz DW, Weiner ID, Hamm LL. Effect of epidermal growth factor on sodium transport in the cortical collecting tubule. Am J Physiol. 1989;256:803–809
  99. Sack E, Taylor Z. High affinity binding sites for epidermal growth factor (EGF) in renal membranes. Biochem Biophys Res Commun. 1988;154:312–317
  100. Wehbi GJ. Early streptozotocin-diabetes mellitus downregulates rat kidney AT2 receptor. Am J Physiol. 2001;280:F254–F265

☆ Supported in part by grants HL-57503 and DK-61400 to Helmy M. Siragy, MD, from the National Institutes of Health. Dr. Siragy was the recipient of the Research Career Development Award K04-HL-03006 from the National Institutes of Health.

PII: S0270-9295(03)00199-2

doi: 10.1016/j.semnephrol.2003.11.009

Seminars in Nephrology
Volume 24, Issue 2 , Pages 93-100 , March 2004

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