Local Angiotensin Generation and AT2 Receptor Activation

  • Joep H.M. Van Esch
  • A.H. Jan Danser
Part of the Proteases in Biology and Disease book series (PBAD, volume 7)


Renin Inhibitor Renin Gene Human Renin Renin Receptor Angiotensin Generation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Abadir, P. M., Carey, R. M. and Siragy, H. M., 2003, Angiotensin AT2 receptors directly stimulate renal nitric oxide in bradykinin B2-receptor-null mice. Hypertension. 42: 600–604.PubMedCrossRefGoogle Scholar
  2. Abadir, P. M., Periasamy, A., Carey, R. M. and Siragy, H. M., 2006, ngiotensin II type 2 receptor-bradykinin B2 receptor functional heterodimerization. Hypertension. 48: 316–322.PubMedCrossRefGoogle Scholar
  3. AbdAlla, S., Lother, H., Abdel-tawab, A. M. and Quitterer, U., 2001, The angiotensin II AT2 receptor is an AT1 receptor antagonist. J Biol Chem. 276: 39721–39726.PubMedCrossRefGoogle Scholar
  4. AbdAlla, S., Lother, H. and Quitterer, U., 2000, AT1-receptor heterodimers show enhanced G-protein activation and altered receptor sequestration. Nature. 407: 94–98.PubMedCrossRefGoogle Scholar
  5. Albiston, A. L., McDowall, S. G., Matsacos, D., Sim, P., Clune, E., Mustafa, T., Lee, J., Mendelsohn, F. A., Simpson, R. J., Connolly, L. M. and Chai, S. Y., 2001, Evidence that the angiotensin IV (AT(4)) receptor is the enzyme insulin-regulated aminopeptidase. J Biol Chem. 276: 48623–48626.PubMedCrossRefGoogle Scholar
  6. Alfakih, K., Lawrance, R. A., Maqbool, A., Walters, K., Ball, S. G., Balmforth, A. J. and Hall, A. S., 2005, The clinical significance of a common, functional, X-linked angiotensin II type 2-receptor gene polymorphism (-1332 G/A) in a cohort of 509 families with premature coronary artery disease. Eur Heart J. 26: 584–589.PubMedCrossRefGoogle Scholar
  7. Ardaillou, R. and Chansel, D., 1997, Synthesis and effects of active fragments of angiotensin II. Kidney Int. 52:1458–1468.PubMedCrossRefGoogle Scholar
  8. Asano, K., Dutcher, D. L., Port, J. D., Minobe, W. A., Tremmel, K. D., Roden, R. L., Bohlmeyer, T. J., Bush, E. W., Jenkin, M. J., Abraham, W. T., Raynolds, M. V., Zisman, L. S., Perryman, M. B. and Bristow, M. R., 1997, Selective downregulation of the angiotensin II AT1-receptor subtype in failing human ventricular myocardium. Circulation. 95: 1193–1200.PubMedGoogle Scholar
  9. Azizi, M., Menard, J., Bissery, A., Guyenne, T. T., Bura-Riviere, A., Vaidyanathan, S. and Camisasca, R. P., 2004, Pharmacologic demonstration of the synergistic effects of a combination of the renin inhibitor aliskiren and the AT1 receptor antagonist valsartan on the angiotensin II-renin feedback interruption. J Am Soc Nephrol. 15: 3126–3133.PubMedCrossRefGoogle Scholar
  10. Batenburg, W. W., Garrelds, I. M., Bernasconi, C. C., Juillerat-Jeanneret, L., van Kats, J. P., Saxena, P. R. and Danser, A. H. J., 2004, Angiotensin II type 2 receptor-mediated vasodilation in human coronary microarteries. Circulation. 109:2296–2301.PubMedCrossRefGoogle Scholar
  11. Bottari, S. P., de Gasparo, M., Steckelings, U. M. and Levens, N. R., 1993, Angiotensin II receptor subtypes: characterization, signalling mechanisms, and possible physiological implications. Front Neuroendocrinol. 14: 123–171.PubMedCrossRefGoogle Scholar
  12. Bove, C. M., Yang, Z., Gilson, W. D., Epstein, F. H., French, B. A., Berr, S. S., Bishop, S. P., Matsubara, H., Carey, R. M. and Kramer, C. M., 2004, Nitric oxide mediates benefits of angiotensin II type 2 receptor overexpression during post-infarct remodeling. Hypertension. 43: 680–685.PubMedCrossRefGoogle Scholar
  13. Brosnihan, K. B., Li, P. and Ferrario, C. M., 1996, Angiotensin-(1-7) dilates canine coronary arteries through kinins and nitric oxide. Hypertension. 27: 523–528.PubMedGoogle Scholar
  14. Burson, J. M., Aguilera, G., Gross, K. W. and Sigmund, C. D., 1994, Differential expression of angiotensin receptor 1A and 1B in mouse. Am J Physiol. 267: E260–267.PubMedGoogle Scholar
  15. Campbell, D. J., Aggarwal, A., Esler, M. and Kaye, D., 2001, beta-blockers, angiotensin II, and ACE inhibitors in patients with heart failure. Lancet. 358: 1609–1610.PubMedCrossRefGoogle Scholar
  16. Campbell, D. J., Alexiou, T., Xiao, H. D., Fuchs, S., McKinley, M. J., Corvol, P. and Bernstein, K. E., 2004, Effect of reduced angiotensin-converting enzyme gene expression and angiotensin-converting enzyme inhibition on angiotensin and bradykinin peptide levels in mice. Hypertension. 43:854–859.PubMedCrossRefGoogle Scholar
  17. Campbell, D. J., Kladis, A. and Duncan, A. M., 1993, Nephrectomy, converting enzyme inhibition, and angiotensin peptides. Hypertension. 22: 513–522.PubMedGoogle Scholar
  18. Castro, C. H., Santos, R. A., Ferreira, A. J., Bader, M., Alenina, N. and Almeida, A. P., 2005, Evidence for a functional interaction of the angiotensin-(1-7) receptor Mas with AT1 and AT2 receptors in the mouse heart. Hypertension. 46: 937–942.PubMedCrossRefGoogle Scholar
  19. Cervenka, L., Maly, J., Karasova, L., Simova, M., Vitko, S., Hellerova, S., Heller, J. and El-Dahr, S. S., 2001, Angiotensin II-induced hypertension in bradykinin B2 receptor knockout mice. Hypertension. 37: 967–973.PubMedGoogle Scholar
  20. Chen, X., Li, W., Yoshida, H., Tsuchida, S., Nishimura, H., Takemoto, F., Okubo, S., Fogo, A., Matsusaka, T. and Ichikawa, I., 1997, Targeting deletion of angiotensin type 1B receptor gene in the mouse. Am J Physiol. 272: F299–304.PubMedGoogle Scholar
  21. Clark, A. F., Sharp, M. G., Morley, S. D., Fleming, S., Peters, J. and Mullins, J. J., 1997, Renin-1 is essential for normal renal juxtaglomerular cell granulation and macula densa morphology. J Biol Chem. 272: 18185–18190.PubMedCrossRefGoogle Scholar
  22. Clausmeyer, S., Reinecke, A., Farrenkopf, R., Unger, T. and Peters, J., 2000, Tissue-specific expression of a rat renin transcript lacking the coding sequence for the prefragment and its stimulation by myocardial infarction. Endocrinology. 141:2963–2970.PubMedCrossRefGoogle Scholar
  23. Crackower, M. A., Sarao, R., Oudit, G. Y., Yagil, C., Kozieradzki, I., Scanga, S. E., Oliveira-dos-Santos, A. J., da Costa, J., Zhang, L., Pei, Y., Scholey, J., Ferrario, C. M., Manoukian, A. S., Chappell, M. C., Backx, P. H., Yagil, Y. and Penninger, J. M., 2002, Angiotensin-converting enzyme 2 is an essential regulator of heart function. Nature. 417: 822–828.PubMedCrossRefGoogle Scholar
  24. Danser, A. H. J. and Deinum, J., 2005, Renin, prorenin and the putative (pro)renin receptor. Hypertension. 46:1069–1076.PubMedCrossRefGoogle Scholar
  25. Danser, A. H. J., van den Dorpel, M. A., Deinum, J., Derkx, F. H., Franken, A. A., Peperkamp, E., de Jong, P. T. and Schalekamp, M. A. D. H., 1989, Renin, prorenin, and immunoreactive renin in vitreous fluid from eyes with and without diabetic retinopathy. J Clin Endocrinol Metab. 68: 160–167.PubMedGoogle Scholar
  26. Danser, A. H. J., van Kats, J. P., Admiraal, P. J., Derkx, F. H., Lamers, J. M., Verdouw, P. D., Saxena, P. R. and Schalekamp, M. A. D. H., 1994, Cardiac renin and angiotensins. Uptake from plasma versus in situ synthesis. Hypertension. 24: 37–48.PubMedGoogle Scholar
  27. de Gasparo, M., Catt, K. J., Inagami, T., Wright, J. W. and Unger, T., 2000, International union of pharmacology. XXIII. The angiotensin II receptors. Pharmacol Rev. 52: 415–472.PubMedGoogle Scholar
  28. de Lannoy, L. M., Danser, A. H. J., Bouhuizen, A. M., Saxena, P. R. and Schalekamp, M. A. D. H., 1998, Localization and production of angiotensin II in the isolated perfused rat heart. Hypertension. 31: 1111–1117.PubMedGoogle Scholar
  29. de Lannoy, L. M., Danser, A. H. J., van Kats, J. P., Schoemaker, R. G., Saxena, P. R. and Schalekamp, M. A. D. H., 1997, Renin-angiotensin system components in the interstitial fluid of the isolated perfused rat heart. Local production of angiotensin I. Hypertension. 29: 1240–1251.PubMedGoogle Scholar
  30. de Lannoy, L. M., Schuijt, M. P., Saxena, P. R., Schalekamp, M. A. D. H. and Danser, A. H. J., 2001, Angiotensin converting enzyme is the main contributor to angiotensin I-II conversion in the interstitium of the isolated perfused rat heart. J Hypertens. 19: 959–965.PubMedCrossRefGoogle Scholar
  31. Deshayes, F. and Nahmias, C., 2005, Angiotensin receptors: a new role in cancer?, Trends Endocrinol Metab. 16: 293–299.PubMedCrossRefGoogle Scholar
  32. Di Bacco, A. and Gill, G., 2003, The secreted glycoprotein CREG inhibits cell growth dependent on the mannose-6-phosphate/insulin-like growth factor II receptor. Oncogene. 22: 5436–5445.PubMedCrossRefGoogle Scholar
  33. Donoghue, M., Hsieh, F., Baronas, E., Godbout, K., Gosselin, M., Stagliano, N., Donovan, M., Woolf, B., Robison, K., Jeyaseelan, R., Breitbart, R. E. and Acton, S., 2000, A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1–9. Circ Res. 87: E1–9.PubMedGoogle Scholar
  34. Doolittle, R. F., 1983, Angiotensinogen is related to the antitrypsin-antithrombin-ovalbumin family. Science. 222:417–419.PubMedCrossRefGoogle Scholar
  35. Duke, L. M., Widdop, R. E., Kett, M. M. and Evans, R. G., 2005, AT(2) receptors mediate tonic renal medullary vasoconstriction in renovascular hypertension. Br J Pharmacol. 144:486–492.PubMedCrossRefGoogle Scholar
  36. Elton, T. S., Stephan, C. C., Taylor, G. R., Kimball, M. G., Martin, M. M., Durand, J. N. and Oparil, S., 1992, Isolation of two distinct type I angiotensin II receptor genes. Biochem Biophys Res Commun. 184: 1067–1073.PubMedCrossRefGoogle Scholar
  37. Esther, C. R., Jr., Howard, T. E., Marino, E. M., Goddard, J. M., Capecchi, M. R. and Bernstein, K. E., 1996, Mice lacking angiotensin-converting enzyme have low blood pressure, renal pathology, and reduced male fertility. Lab Invest. 74:953–965.PubMedGoogle Scholar
  38. Fujita, M., Hayashi, I., Yamashina, S., Itoman, M. and Majima, M., 2002, Blockade of angiotensin AT1a receptor signaling reduces tumor growth, angiogenesis, and metastasis. Biochem Biophys Res Commun. 294: 441–447.PubMedCrossRefGoogle Scholar
  39. Fukamizu, A., Sugimura, K., Takimoto, E., Sugiyama, F., Seo, M. S., Takahashi, S., Hatae, T., Kajiwara, N., Yagami, K. and Murakami, K., 1993, Chimeric renin-angiotensin system demonstrates sustained increase in blood pressure of transgenic mice carrying both human renin and human angiotensinogen genes. J Biol Chem. 268:11617–11621.PubMedGoogle Scholar
  40. Gradman, A. H., Schmieder, R. E., Lins, R. L., Nussberger, J., Chiang, Y. and Bedigian, M. P., 2005, Aliskiren, a novel orally effective renin inhibitor, provides dose-dependent antihypertensive efficacy and placebo-like tolerability in hypertensive patients. Circulation. 111: 1012–1018.PubMedCrossRefGoogle Scholar
  41. Guimaraes, S. and Pinheiro, H., 2005, Functional evidence that in the cardiovascular system AT1 angiotensin II receptors are AT1B prejunctionally and AT1A postjunctionally. Cardiovasc Res. 67: 208–215.PubMedCrossRefGoogle Scholar
  42. Gurley, S. B., Allred, A., Le, T. H., Griffiths, R., Mao, L., Philip, N., Haystead, T. A., Donoghue, M., Breitbart, R. E., Acton, S. L., Rockman, H. A. and Coffman, T. M., 2006, Altered blood pressure responses and normal cardiac phenotype in ACE2-null mice. J Clin Invest. 116: 2218–2225.PubMedCrossRefGoogle Scholar
  43. Hackenthal, E., Hackenthal, R. and Hilgenfeldt, U., 1978, Isorenin, pseudorenin, cathepsin D and renin. A comparative enzymatic study of angiotensin-forming enzymes. Biochim Biophys Acta. 522:574–588.PubMedGoogle Scholar
  44. Hashimoto, N., Maeshima, Y., Satoh, M., Odawara, M., Sugiyama, H., Kashihara, N., Matsubara, H., Yamasaki, Y. and Makino, H., 2004, Overexpression of angiotensin type 2 receptor ameliorates glomerular injury in a mouse remnant kidney model. Am J Physiol Renal Physiol. 286: F516–525.PubMedCrossRefGoogle Scholar
  45. Hein, L., Barsh, G. S., Pratt, R. E., Dzau, V. J. and Kobilka, B. K., 1995, Behavioural and cardiovascular effects of disrupting the angiotensin II type-2 receptor in mice. Nature. 377:744–747.PubMedCrossRefGoogle Scholar
  46. Herrmann, S. M., Nicaud, V., Schmidt-Petersen, K., Pfeifer, J., Erdmann, J., McDonagh, T., Dargie, H. J., Paul, M. and Regitz-Zagrosek, V., 2002, Angiotensin II type 2 receptor gene polymorphism and cardiovascular phenotypes: the GLAECO and GLAOLD studies. Eur J Heart Fail. 4: 707–712.PubMedCrossRefGoogle Scholar
  47. Hiyoshi, H., Yayama, K., Takano, M. and Okamoto, H., 2005, Angiotensin type 2 receptor-mediated phosphorylation of eNOS in the aortas of mice with 2-kidney, 1-clip hypertension. Hypertension. 45: 967–973.PubMedCrossRefGoogle Scholar
  48. Horiuchi, M., Akishita, M. and Dzau, V. J., 1998, Molecular and cellular mechanism of angiotensin II-mediated apoptosis. Endocr Res. 24: 307–314.PubMedCrossRefGoogle Scholar
  49. Hubert, C., Houot, A. M., Corvol, P. and Soubrier, F., 1991, Structure of the angiotensin I-converting enzyme gene. Two alternate promoters correspond to evolutionary steps of a duplicated gene. J Biol Chem. 266: 15377–15383.PubMedGoogle Scholar
  50. Ichihara, A., Hayashi, M., Kaneshiro, Y., Suzuki, F., Nakagawa, T., Tada, Y., Koura, Y., Nishiyama, A., Okada, H., Uddin, M. N., Nabi, A. H., Ishida, Y., Inagami, T. and Saruta, T., 2004, Inhibition of diabetic nephropathy by a decoy peptide corresponding to the “handle” region for nonproteolytic activation of prorenin. J Clin Invest. 114: 1128–1135.PubMedCrossRefGoogle Scholar
  51. Ichihara, S., Senbonmatsu, T., Price, E., Jr., Ichiki, T., Gaffney, F. A. and Inagami, T., 2001, Angiotensin II type 2 receptor is essential for left ventricular hypertrophy and cardiac fibrosis in chronic angiotensin II-induced hypertension. Circulation. 104: 346–351.PubMedGoogle Scholar
  52. Ichiki, T., Labosky, P. A., Shiota, C., Okuyama, S., Imagawa, Y., Fogo, A., Niimura, F., Ichikawa, I., Hogan, B. L. and Inagami, T., 1995, Effects on blood pressure and exploratory behaviour of mice lacking angiotensin II type-2 receptor. Nature. 377:748–750.PubMedCrossRefGoogle Scholar
  53. Ito, M., Oliverio, M. I., Mannon, P. J., Best, C. F., Maeda, N., Smithies, O. and Coffman, T. M., 1995, Regulation of blood pressure by the type 1A angiotensin II receptor gene. Proc Natl Acad Sci U S A. 92: 3521–3525.PubMedCrossRefGoogle Scholar
  54. Itskovitz, J., Rubattu, S., Levron, J. and Sealey, J. E., 1992, Highest concentrations of prorenin and human chorionic gonadotropin in gestational sacs during early human pregnancy. J Clin Endocrinol Metab. 75: 906–910.PubMedCrossRefGoogle Scholar
  55. Jin, X. Q., Fukuda, N., Su, J. Z., Lai, Y. M., Suzuki, R., Tahira, Y., Takagi, H., Ikeda, Y., Kanmatsuse, K. and Miyazaki, H., 2002, Angiotensin II type 2 receptor gene transfer downregulates angiotensin II type 1a receptor in vascular smooth muscle cells. Hypertension. 39: 1021–1027.PubMedCrossRefGoogle Scholar
  56. Kageyama, R., Ohkubo, H. and Nakanishi, S., 1985, Induction of rat liver angiotensinogen mRNA following acute inflammation. Biochem Biophys Res Commun. 129: 826–832.PubMedCrossRefGoogle Scholar
  57. Kang, J. X., Li, Y. and Leaf, A., 1997, Mannose-6-phosphate/insulin-like growth factor-II receptor is a receptor for retinoic acid. Proc Natl Acad Sci U S A. 94:13671–13676.PubMedCrossRefGoogle Scholar
  58. Katada, J. and Majima, M., 2002, AT(2) receptor-dependent vasodilation is mediated by activation of vascular kinin generation under flow conditions. Br J Pharmacol. 136:484–491.PubMedCrossRefGoogle Scholar
  59. Katz, S. A., Opsahl, J. A., Lunzer, M. M., Forbis, L. M. and Hirsch, A. T., 1997, Effect of bilateral nephrectomy on active renin, angiotensinogen, and renin glycoforms in plasma and myocardium. Hypertension. 30: 259–266.PubMedGoogle Scholar
  60. Keller, S. R., Scott, H. M., Mastick, C. C., Aebersold, R. and Lienhard, G. E., 1995, Cloning and characterization of a novel insulin-regulated membrane aminopeptidase from Glut4 vesicles. J Biol Chem. 270: 23612–23618.PubMedCrossRefGoogle Scholar
  61. Kessler, S. P., Senanayake, P. D., Gaughan, C. and Sen, G. C., 2007, Vascular expression of germinal ACE fails to maintain normal blood pressure in ACE-/- mice. FASEB J. 21: 156–166.PubMedCrossRefGoogle Scholar
  62. Kimura, S., Mullins, J. J., Bunnemann, B., Metzger, R., Hilgenfeldt, U., Zimmermann, F., Jacob, H., Fuxe, K., Ganten, D. and Kaling, M., 1992, High blood pressure in transgenic mice carrying the rat angiotensinogen gene. EMBO J. 11:821–827.PubMedGoogle Scholar
  63. Kitamura, N., Ohkubo, H. and Nakanishi, S., 1987, Molecular biology of the angiotensinogen and kininogen genes. J Cardiovasc Pharmacol. 10 (suppl 7): S49–53.PubMedCrossRefGoogle Scholar
  64. Klett, C., Nobiling, R., Gierschik, P. and Hackenthal, E., 1993, Angiotensin II stimulates the synthesis of angiotensinogen in hepatocytes by inhibiting adenylylcyclase activity and stabilizing angiotensinogen mRNA. J Biol Chem. 268: 25095–25107.PubMedGoogle Scholar
  65. Kornfeld, S., 1992, Structure and function of the mannose 6-phosphate/insulinlike growth factor II receptors. Annu Rev Biochem. 61: 307–330.PubMedCrossRefGoogle Scholar
  66. Krege, J. H., John, S. W., Langenbach, L. L., Hodgin, J. B., Hagaman, J. R., Bachman, E. S., Jennette, J. C., O’Brien, D. A. and Smithies, O., 1995, Male-female differences in fertility and blood pressure in ACE-deficient mice. Nature. 375:146–148.PubMedCrossRefGoogle Scholar
  67. Lemos, V. S., Silva, D. M., Walther, T., Alenina, N., Bader, M. and Santos, R. A., 2005, The endothelium-dependent vasodilator effect of the nonpeptide Ang(1-7) mimic AVE 0991 is abolished in the aorta of mas-knockout mice. J Cardiovasc Pharmacol. 46: 274–279.PubMedCrossRefGoogle Scholar
  68. Lenz, T., Sealey, J. E., Lappe, R. W., Carilli, C., Oshiro, G. T., Baxter, J. D. and Laragh, J. H., 1990, Infusion of recombinant human prorenin into rhesus monkeys. Effects on hemodynamics, renin-angiotensin-aldosterone axis and plasma testosterone. Am J Hypertens. 3: 257–261.PubMedGoogle Scholar
  69. Li, W., Moore, M. J., Vasilieva, N., Sui, J., Wong, S. K., Berne, M. A., Somasundaran, M., Sullivan, J. L., Luzuriaga, K., Greenough, T. C., Choe, H. and Farzan, M., 2003, Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 426: 450–454.PubMedCrossRefGoogle Scholar
  70. Li, X. C. and Widdop, R. E., 2004, AT2 receptor-mediated vasodilatation is unmasked by AT1 receptor blockade in conscious SHR. Br J Pharmacol. 142: 821–830.PubMedCrossRefGoogle Scholar
  71. Liu, Y. H., Xu, J., Yang, X. P., Yang, F., Shesely, E. and Carretero, O. A., 2002, Effect of ACE inhibitors and angiotensin II type 1 receptor antagonists on endothelial NO synthase knockout mice with heart failure. Hypertension. 39: 375–381.PubMedCrossRefGoogle Scholar
  72. Mehta, P. K. and Griendling, K. K., 2007, Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system. Am J Physiol Cell Physiol. 292: C82–97.PubMedCrossRefGoogle Scholar
  73. Metzger, R., Bader, M., Ludwig, T., Berberich, C., Bunnemann, B. and Ganten, D., 1995, Expression of the mouse and rat mas proto-oncogene in the brain and peripheral tissues. FEBS Lett. 357:27–32.PubMedCrossRefGoogle Scholar
  74. Morris, B. J., 1992, Molecular biology of renin. I: Gene and protein structure, synthesis and processing. J Hypertens. 10: 209–214.PubMedCrossRefGoogle Scholar
  75. Mukoyama, M., Nakajima, M., Horiuchi, M., Sasamura, H., Pratt, R. E. and Dzau, V. J., 1993, Expression cloning of type 2 angiotensin II receptor reveals a unique class of seven-transmembrane receptors. J Biol Chem. 268: 24539–24542.PubMedGoogle Scholar
  76. Müller, D. N., Fischli, W., Clozel, J. P., Hilgers, K. F., Bohlender, J., Menard, J., Busjahn, A., Ganten, D. and Luft, F. C., 1998, Local angiotensin II generation in the rat heart: role of renin uptake. Circ Res. 82: 13–20.PubMedGoogle Scholar
  77. Murphy, T. J., Alexander, R. W., Griendling, K. K., Runge, M. S. and Bernstein, K. E., 1991, Isolation of a cDNA encoding the vascular type-1 angiotensin II receptor. Nature. 351:233–236.PubMedCrossRefGoogle Scholar
  78. Nguyen, G., Delarue, F., Burckle, C., Bouzhir, L., Giller, T. and Sraer, J. D., 2002, Pivotal role of the renin/prorenin receptor in angiotensin II production and cellular responses to renin. J Clin Invest. 109: 1417–1427.PubMedCrossRefGoogle Scholar
  79. Niimura, F., Labosky, P. A., Kakuchi, J., Okubo, S., Yoshida, H., Oikawa, T., Ichiki, T., Naftilan, A. J., Fogo, A., Inagami, T. and et al., 1995, Gene targeting in mice reveals a requirement for angiotensin in the development and maintenance of kidney morphology and growth factor regulation. J Clin Invest. 96:2947–2954.PubMedGoogle Scholar
  80. Nouet, S. and Nahmias, C., 2000, Signal transduction from the angiotensin II AT2 receptor. Trends Endocrinol Metab. 11:1–6.PubMedCrossRefGoogle Scholar
  81. Nussberger, J., Wuerzner, G., Jensen, C. and Brunner, H. R., 2002, Angiotensin II suppression in humans by the orally active renin inhibitor Aliskiren (SPP100): comparison with enalapril. Hypertension. 39: E1–8.PubMedCrossRefGoogle Scholar
  82. Oliverio, M. I., Best, C. F., Kim, H. S., Arendshorst, W. J., Smithies, O. and Coffman, T. M., 1997, Angiotensin II responses in AT1A receptor-deficient mice: a role for AT1B receptors in blood pressure regulation. Am J Physiol. 272: F515–520.PubMedGoogle Scholar
  83. Padia, S. H., Howell, N. L., Siragy, H. M. and Carey, R. M., 2006, Renal angiotensin type 2 receptors mediate natriuresis via angiotensin III in the angiotensin II type 1 receptor-blocked rat. Hypertension. 47: 537–544.PubMedCrossRefGoogle Scholar
  84. Patel, J. M., Martens, J. R., Li, Y. D., Gelband, C. H., Raizada, M. K. and Block, E. R., 1998, Angiotensin IV receptor-mediated activation of lung endothelial NOS is associated with vasorelaxation. Am J Physiol. 275: L1061–1068.PubMedGoogle Scholar
  85. Paul, M., Poyan Mehr, A. and Kreutz, R., 2006, Physiology of local renin-angiotensin systems. Physiol Rev. 86: 747–803.PubMedCrossRefGoogle Scholar
  86. Perlegas, D., Xie, H., Sinha, S., Somlyo, A. V. and Owens, G. K., 2005, ANG II type 2 receptor regulates smooth muscle growth and force generation in late fetal mouse development. Am J Physiol Heart Circ Physiol. 288: H96–102.PubMedCrossRefGoogle Scholar
  87. Peters, J., Farrenkopf, R., Clausmeyer, S., Zimmer, J., Kantachuvesiri, S., Sharp, M. G. and Mullins, J. J., 2002, Functional significance of prorenin internalization in the rat heart. Circ Res. 90: 1135–1141.PubMedCrossRefGoogle Scholar
  88. Purdy, R. E. and Weber, M. A., 1988, Angiotensin II amplification of alpha-adrenergic vasoconstriction: role of receptor reserve. Circ Res. 63: 748–757.PubMedGoogle Scholar
  89. Ritter, O., Schuh, K., Brede, M., Rothlein, N., Burkard, N., Hein, L. and Neyses, L., 2003, AT2 receptor activation regulates myocardial eNOS expression via the calcineurin-NF-AT pathway. Faseb J. 17: 283–285.PubMedGoogle Scholar
  90. Ruiz-Ortega, M., Esteban, V., Suzuki, Y., Ruperez, M., Mezzano, S., Ardiles, L., Justo, P., Ortiz, A. and Egido, J., 2003, Renal expression of angiotensin type 2 (AT2) receptors during kidney damage. Kidn Int. 86: S21–26.CrossRefGoogle Scholar
  91. Santos, R. A. S., Campagnole-Santos, M. J. and Andrade, S. P., 2000, Angiotensin-(1–7): an update. Regul Pept. 91:45–62.PubMedCrossRefGoogle Scholar
  92. Santos, R. A. S., Castro, C. H., Gava, E., Pinheiro, S. V., Almeida, A. P., Paula, R. D., Cruz, J. S., Ramos, A. S., Rosa, K. T., Irigoyen, M. C., Bader, M., Alenina, N., Kitten, G. T. and Ferreira, A. J., 2006, Impairment of in vitro and in vivo heart function in angiotensin-(1–7) receptor MAS knockout mice. Hypertension. 47: 996–1002.PubMedCrossRefGoogle Scholar
  93. Santos, R. A. S., Simoes e Silva, A. C., Maric, C., Silva, D. M., Machado, R. P., de Buhr, I., Heringer-Walther, S., Pinheiro, S. V., Lopes, M. T., Bader, M., Mendes, E. P., Lemos, V. S., Campagnole-Santos, M. J., Schultheiss, H. P., Speth, R. and Walther, T., 2003, Angiotensin-(1–7) is an endogenous ligand for the G protein-coupled receptor Mas. Proc Natl Acad Sci U S A. 100: 8258–8263.PubMedCrossRefGoogle Scholar
  94. Saris, J. J., Derkx, F. H. M., de Bruin, R. J. A., Dekkers, D. H., Lamers, J. M., Saxena, P. R., Schalekamp, M. A. D. H. and Danser, A. H. J., 2001, High-affinity prorenin binding to cardiac man-6-P/IGF-II receptors precedes proteolytic activation to renin. Am J Physiol Heart Circ Physiol. 280: H1706–1715.PubMedGoogle Scholar
  95. Saris, J. J., t Hoen, P. A., Garrelds, I. M., Dekkers, D. H., den Dunnen, J. T., Lamers, J. M. and Danser, A. H. J., 2006, Prorenin induces intracellular signaling in cardiomyocytes independently of angiotensin II. Hypertension. 48: 564–571.PubMedCrossRefGoogle Scholar
  96. Saris, J. J., van Dijk, M. A., Kroon, I., Schalekamp, M. A. D. H. and Danser, A. H. J., 2000, Functional importance of angiotensin-converting enzyme-dependent in situ angiotensin II generation in the human forearm. Hypertension. 35:764–768.PubMedGoogle Scholar
  97. Sasaki, K., Yamano, Y., Bardhan, S., Iwai, N., Murray, J. J., Hasegawa, M., Matsuda, Y. and Inagami, T., 1991, Cloning and expression of a complementary DNA encoding a bovine adrenal angiotensin II type-1 receptor. Nature. 351: 230–233.PubMedCrossRefGoogle Scholar
  98. Savoia, C., Touyz, R. M., Volpe, M. and Schiffrin, E. L., 2007, Angiotensin type 2 receptor in resistance arteries of type 2 diabetic hypertensive patients. Hypertension. 49: 341–346.PubMedCrossRefGoogle Scholar
  99. Schieffer, B., Wirger, A., Meybrunn, M., Seitz, S., Holtz, J., Riede, U. N. and Drexler, H., 1994, Comparative effects of chronic angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor blockade on cardiac remodeling after myocardial infarction in the rat. Circulation. 89: 2273–2282.PubMedGoogle Scholar
  100. Schmieder, R. E., Erdmann, J., Delles, C., Jacobi, J., Fleck, E., Hilgers, K. and Regitz-Zagrosek, V., 2001, Effect of the angiotensin II type 2-receptor gene (+1675 G/A) on left ventricular structure in humans. J Am Coll Cardiol. 37:175–182.PubMedCrossRefGoogle Scholar
  101. Schneider, M. D. and Lorell, B. H., 2001, AT(2), judgment day: which angiotensin receptor is the culprit in cardiac hypertrophy?, Circulation. 104: 247–248.PubMedGoogle Scholar
  102. Schuijt, M. P., Basdew, M., van Veghel, R., de Vries, R., Saxena, P. R., Schoemaker, R. G. and Danser, A. H. J., 2001, AT(2) receptor-mediated vasodilation in the heart: effect of myocardial infarction. Am J Physiol Heart Circ Physiol. 281:H2590–2596.PubMedGoogle Scholar
  103. Schuijt, M. P. and Danser, A. H. J., 2002, Cardiac angiotensin II: an intracrine hormone?, Am J Hypertens. 15: 1109–1116.PubMedCrossRefGoogle Scholar
  104. Schuijt, M. P., van Kats, J. P., de Zeeuw, S., Duncker, D. J., Verdouw, P. D., Schalekamp, M. A. D. H. and Danser, A. H. J., 1999, Cardiac interstitial fluid levels of angiotensin I and II in the pig. J Hypertens. 17: 1885–1891.PubMedCrossRefGoogle Scholar
  105. Sealey, J. E., Goldstein, M., Pitarresi, T., Kudlak, T. T., Glorioso, N., Fiamengo, S. A. and Laragh, J. H., 1988, Prorenin secretion from human testis: no evidence for secretion of active renin or angiotensinogen. J Clin Endocrinol Metab. 66:974–978.PubMedCrossRefGoogle Scholar
  106. Senbonmatsu, T., Ichihara, S., Price, E., Jr., Gaffney, F. A. and Inagami, T., 2000, Evidence for angiotensin II type 2 receptor-mediated cardiac myocyte enlargement during in vivo pressure overload. J Clin Invest. 106: R25–29.PubMedGoogle Scholar
  107. Sharp, M. G., Fettes, D., Brooker, G., Clark, A. F., Peters, J., Fleming, S. and Mullins, J. J., 1996, Targeted inactivation of the Ren-2 gene in mice. Hypertension. 28: 1126–1131.PubMedGoogle Scholar
  108. Shinagawa, T., Do, Y. S., Baxter, J. and Hsueh, W. A., 1992, Purification and characterization of human truncated prorenin. Biochemistry. 31: 2758–2764.PubMedCrossRefGoogle Scholar
  109. Silvestre, J. S., Tamarat, R., Senbonmatsu, T., Icchiki, T., Ebrahimian, T., Iglarz, M., Besnard, S., Duriez, M., Inagami, T. and Levy, B. I., 2002, Antiangiogenic effect of angiotensin II type 2 receptor in ischemia-induced angiogenesis in mice hindlimb. Circ Res. 90: 1072–1079.PubMedCrossRefGoogle Scholar
  110. Siragy, H. M. and Carey, R. M., 1997, The subtype 2 (AT2) angiotensin receptor mediates renal production of nitric oxide in conscious rats. J Clin Invest. 100: 264–269.PubMedGoogle Scholar
  111. Siragy, H. M., Xue, C., Abadir, P. and Carey, R. M., 2005, Angiotensin subtype-2 receptors inhibit renin biosynthesis and angiotensin II formation. Hypertension. 45: 133–137.PubMedGoogle Scholar
  112. Stegbauer, J., Vonend, O., Oberhauser, V. and Rump, L. C., 2003, Effects of angiotensin-(1–7) and other bioactive components of the renin-angiotensin system on vascular resistance and noradrenaline release in rat kidney. J Hypertens. 21: 1391–1399.PubMedCrossRefGoogle Scholar
  113. Sugaya, T., Nishimatsu, S., Tanimoto, K., Takimoto, E., Yamagishi, T., Imamura, K., Goto, S., Imaizumi, K., Hisada, Y., Otsuka, A. and et al., 1995, Angiotensin II type 1a receptor-deficient mice with hypotension and hyperreninemia. J Biol Chem. 270:18719–18722.PubMedCrossRefGoogle Scholar
  114. Suzuki, F., Hayakawa, M., Nakagawa, T., Nasir, U. M., Ebihara, A., Iwasawa, A., Ishida, Y., Nakamura, Y. and Murakami, K., 2003, Human prorenin has “gate and handle” regions for its non-proteolytic activation. J Biol Chem. 278:22217–22222.PubMedCrossRefGoogle Scholar
  115. Swanson, G. N., Hanesworth, J. M., Sardinia, M. F., Coleman, J. K., Wright, J. W., Hall, K. L., Miller-Wing, A. V., Stobb, J. W., Cook, V. I., Harding, E. C. and et al., 1992, Discovery of a distinct binding site for angiotensin II (3–8), a putative angiotensin IV receptor. Regul Pept. 40: 409–419.PubMedCrossRefGoogle Scholar
  116. Tanaka, M., Tsuchida, S., Imai, T., Fujii, N., Miyazaki, H., Ichiki, T., Naruse, M. and Inagami, T., 1999, Vascular response to angiotensin II is exaggerated through an upregulation of AT1 receptor in AT2 knockout mice. Biochem Biophys Res Commun. 258: 194–198.PubMedCrossRefGoogle Scholar
  117. Tanimoto, K., Sugiyama, F., Goto, Y., Ishida, J., Takimoto, E., Yagami, K., Fukamizu, A. and Murakami, K., 1994, Angiotensinogen-deficient mice with hypotension. J Biol Chem. 269: 31334–31337.PubMedGoogle Scholar
  118. Thomas, W. G., Thekkumkara, T. J. and Baker, K. M., 1996, Molecular mechanisms of angiotensin II (AT1A) receptor endocytosis. Clin Exp Pharmacol Physiol. 3:S74–80.Google Scholar
  119. Tom, B., de Vries, R., Saxena, P. R. and Danser, A. H. J., 2001, Bradykinin potentiation by angiotensin-(1–7) and ACE inhibitors correlates with ACE C- and N-domain blockade. Hypertension. 38: 95–99.PubMedGoogle Scholar
  120. Tom, B., Garrelds, I. M., Scalbert, E., Stegmann, A. P., Boomsma, F., Saxena, P. R. and Danser, A. H. J., 2003, ACE-versus chymase-dependent angiotensin II generation in human coronary arteries: a matter of efficiency?, Arterioscler Thromb Vasc Biol. 23: 251–256.PubMedCrossRefGoogle Scholar
  121. Tsuchida, S., Matsusaka, T., Chen, X., Okubo, S., Niimura, F., Nishimura, H., Fogo, A., Utsunomiya, H., Inagami, T. and Ichikawa, I., 1998, Murine double nullizygotes of the angiotensin type 1A and 1B receptor genes duplicate severe abnormal phenotypes of angiotensinogen nullizygotes. J Clin Invest. 101:755–760.PubMedGoogle Scholar
  122. Tsutsumi, Y., Matsubara, H., Masaki, H., Kurihara, H., Murasawa, S., Takai, S., Miyazaki, M., Nozawa, Y., Ozono, R., Nakagawa, K., Miwa, T., Kawada, N., Mori, Y., Shibasaki, Y., Tanaka, Y., Fujiyama, S., Koyama, Y., Fujiyama, A., Takahashi, H. and Iwasaka, T., 1999, Angiotensin II type 2 receptor overexpression activates the vascular kinin system and causes vasodilation. J Clin Invest. 104:925–935.PubMedGoogle Scholar
  123. Turner, A. J. and Hooper, N. M., 2002, The angiotensin-converting enzyme gene family: genomics and pharmacology. Trends Pharmacol Sci. 23: 177–183.PubMedCrossRefGoogle Scholar
  124. Urata, H., Kinoshita, A., Misono, K. S., Bumpus, F. M. and Husain, A., 1990, Identification of a highly specific chymase as the major angiotensin II-forming enzyme in the human heart. J Biol Chem. 265: 22348–22357.PubMedGoogle Scholar
  125. van den Eijnden, M. M. E. D., de Bruin, R. J. A., de Wit, E., Sluiter, W., Deinum, J., Reudelhuber, T. L. and Danser, A. H. J., 2002, Transendothelial transport of renin-angiotensin system components. J Hypertens. 20: 2029–2037.PubMedCrossRefGoogle Scholar
  126. van Esch, J. H. M., Schuijt, M. P., Sayed, J., Choudhry, Y., Walther, T. and Danser, A. H. J., 2006, AT(2) receptor-mediated vasodilation in the mouse heart depends on AT(1A) receptor activation. Br J Pharmacol. 148: 452–458.PubMedCrossRefGoogle Scholar
  127. van Esch, J. H. M., Tom, B., Dive, V., Batenburg, W. W., Georgiadis, D., Yiotakis, A., van Gool, J. M., de Bruijn, R. J. A., de Vries, R. and Danser, A. H. J., 2005, Selective angiotensin-converting enzyme C-domain inhibition is sufficient to prevent angiotensin I-induced vasoconstriction. Hypertension. 45: 120–125.PubMedGoogle Scholar
  128. van Kats, J. P., Chai, W., Duncker, D. J., Schalekamp, M. A. D. H. and Danser, A. H. J., 2005, Adrenal angiotensin: origin and site of generation. Am J Hypertens. 18: 1104–1110.PubMedCrossRefGoogle Scholar
  129. van Kats, J. P., de Lannoy, L. M., Danser, A. H. J., van Meegen, J. R., Verdouw, P. D. and Schalekamp, M. A. D. H., 1997, Angiotensin II type 1 (AT1) receptor-mediated accumulation of angiotensin II in tissues and its intracellular half-life in vivo. Hypertension. 30: 42–49.PubMedGoogle Scholar
  130. van Kats, J. P., Duncker, D. J., Haitsma, D. B., Schuijt, M. P., Niebuur, R., Stubenitsky, R., Boomsma, F., Schalekamp, M. A. D. H., Verdouw, P. D. and Danser, A. H. J., 2000, Angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor blockade prevent cardiac remodeling in pigs after myocardial infarction: role of tissue angiotensin II. Circulation. 102: 1556–1563.PubMedGoogle Scholar
  131. van Kats, J. P., van Meegen, J. R., Verdouw, P. D., Duncker, D. J., Schalekamp, M. A. D. H. and Danser, A. H. J., 2001, Subcellular localization of angiotensin II in kidney and adrenal. J Hypertens. 19: 583–589.PubMedCrossRefGoogle Scholar
  132. van Rodijnen, W. F., van Lambalgen, T. A., van Wijhe, M. H., Tangelder, G. J. and Ter Wee, P. M., 2002, Renal microvascular actions of angiotensin II fragments. Am J Physiol Renal Physiol. 283: F86–92.PubMedGoogle Scholar
  133. Véniant, M., Ménard, J., Bruneval, P., Morley, S., Gonzales, M. F. and Mullins, J. J., 1996, Vascular damage without hypertension in transgenic rats expressing prorenin exclusively in the liver. J Clin Invest. 98: 1966–1970.PubMedCrossRefGoogle Scholar
  134. Vickers, C., Hales, P., Kaushik, V., Dick, L., Gavin, J., Tang, J., Godbout, K., Parsons, T., Baronas, E., Hsieh, F., Acton, S., Patane, M., Nichols, A. and Tummino, P., 2002, Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase. J Biol Chem. 277: 14838–14843.PubMedCrossRefGoogle Scholar
  135. Walters, P. E., Gaspari, T. A. and Widdop, R. E., 2005, Angiotensin-(1–7) acts as a vasodepressor agent via angiotensin II type 2 receptors in conscious rats. Hypertension. 45:960–966.PubMedCrossRefGoogle Scholar
  136. Walther, T., Menrad, A., Orzechowski, H. D., Siemeister, G., Paul, M. and Schirner, M., 2003, Differential regulation of in vivo angiogenesis by angiotensin II receptors. FASEB J. 17:2061–2067.PubMedCrossRefGoogle Scholar
  137. Wei, L., Alhenc-Gelas, F., Corvol, P. and Clauser, E., 1991a, The two homologous domains of human angiotensin I-converting enzyme are both catalytically active. J Biol Chem. 266:9002–9008.Google Scholar
  138. Wei, L., Alhenc-Gelas, F., Soubrier, F., Michaud, A., Corvol, P. and Clauser, E., 1991b, Expression and characterization of recombinant human angiotensin I-converting enzyme. Evidence for a C-terminal transmembrane anchor and for a proteolytic processing of the secreted recombinant and plasma enzymes. J Biol Chem. 266: 5540–5546.Google Scholar
  139. Wharton, J., Morgan, K., Rutherford, R. A., Catravas, J. D., Chester, A., Whitehead, B. F., De Leval, M. R., Yacoub, M. H. and Polak, J. M., 1998, Differential distribution of angiotensin AT2 receptors in the normal and failing human heart. J Pharmacol Exp Ther. 284: 323–336.PubMedGoogle Scholar
  140. Widdop, R. E., Jones, E. S., Hannan, R. E. and Gaspari, T. A., 2003, Angiotensin AT2 receptors: cardiovascular hope or hype?, Br J Pharmacol. 140: 809–824.PubMedCrossRefGoogle Scholar
  141. Widdop, R. E., Matrougui, K., Levy, B. I. and Henrion, D., 2002, AT2 receptor-mediated relaxation is preserved after long-term AT1 receptor blockade. Hypertension. 40: 516–520.PubMedCrossRefGoogle Scholar
  142. Wiemer, G., Schölkens, B. A., Wagner, A., Heitsch, H. and Linz, W., 1993, The possible role of angiotensin II subtype AT2 receptors in endothelial cells and isolated ischemic rat hearts. J Hypertens. 11: S234–235.CrossRefGoogle Scholar
  143. Wright, J. W. and Harding, J. W., 1995, Brain angiotensin receptor subtypes AT1, AT2, and AT4 and their functions. Regul Pept. 59: 269–295.PubMedCrossRefGoogle Scholar
  144. Wright, J. W., Stubley, L., Pederson, E. S., Kramar, E. A., Hanesworth, J. M. and Harding, J. W., 1999, Contributions of the brain angiotensin IV-AT4 receptor subtype system to spatial learning. J Neurosci. 19: 3952–3961.PubMedGoogle Scholar
  145. Wu, J. N., Edwards, D. and Berecek, K. H., 1994, Changes in renal angiotensin II receptors in spontaneously hypertensive rats by early treatment with the angiotensin-converting enzyme inhibitor captopril. Hypertension. 23: 819–822.PubMedGoogle Scholar
  146. Xu, J., Carretero, O.A., Liu, Y.H., Shesely, E.G., Yang, F., Kapke, A. and Yang, X.P., 2002, Role of AT2 receptors in the cardioprotective effect of AT1 antagonists in mice. Hypertension. 40: 244–250.PubMedCrossRefGoogle Scholar
  147. Yamada, H., Akishita, M., Ito, M., Tamura, K., Daviet, L., Lehtonen, J. Y., Dzau, V. J. and Horiuchi, M., 1999, AT2 receptor and vascular smooth muscle cell differentiation in vascular development. Hypertension. 33: 1414–1419.PubMedGoogle Scholar
  148. Yang, Z., Bove, C. M., French, B. A., Epstein, F. H., Berr, S. S., DiMaria, J. M., Gibson, J. J., Carey, R. M. and Kramer, C. M., 2002, Angiotensin II type 2 receptor overexpression preserves left ventricular function after myocardial infarction. Circulation. 106: 106–111.PubMedCrossRefGoogle Scholar
  149. Yayama, K., Horii, M., Hiyoshi, H., Takano, M., Okamoto, H., Kagota, S. and Kunitomo, M., 2004, Up-regulation of angiotensin II type 2 receptor in rat thoracic aorta by pressure-overload. J Pharmacol Exp Ther. 308: 736–743.PubMedCrossRefGoogle Scholar
  150. Zhou, Y., Chen, Y., Dirksen, W. P., Morris, M. and Periasamy, M., 2003, AT1b receptor predominantly mediates contractions in major mouse blood vessels. Circ Res. 93: 1089–1094.PubMedCrossRefGoogle Scholar
  151. Zini, S., Fournie-Zaluski, M. C., Chauvel, E., Roques, B. P., Corvol, P. and Llorens-Cortes, C., 1996, Identification of metabolic pathways of brain angiotensin II and III using specific aminopeptidase inhibitors: predominant role of angiotensin III in the control of vasopressin release. Proc Natl Acad Sci U S A. 93: 11968–11973.PubMedCrossRefGoogle Scholar
  152. Zou, Y., Akazawa, H., Qin, Y., Sano, M., Takano, H., Minamino, T., Makita, N., Iwanaga, K., Zhu, W., Kudoh, S., Toko, H., Tamura, K., Kihara, M., Nagai, T., Fukamizu, A., Umemura, S., Iiri, T., Fujita, T. and Komuro, I., 2004, Mechanical stress activates angiotensin II type 1 receptor without the involvement of angiotensin II. Nat Cell Biol. 6: 499–506.PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2007

Authors and Affiliations

  • Joep H.M. Van Esch
    • 1
  • A.H. Jan Danser
    • 1
  1. 1.Department of PharmacologyErasmus MCRotterdamThe Netherlands

Personalised recommendations