About this Journal Submit a Manuscript Table of Contents 
International Journal of Hypertension
Volume 2012 (2012), Article ID 124758, 12 pages
doi:10.1155/2012/124758
Review Article

Focus on Brain Angiotensin III and Aminopeptidase A in the Control of Hypertension

John W. Wright,1 Shigehiko Mizutani,2 and Joseph W. Harding1

1Departments of Psychology and Veterinary and Comparative Anatomy, Pharmacology, and Physiology and Programs in Neuroscience and Biotechnology, Washington State University, P.O. Box 644820, Pullman, WA 99164-4820, USA
2Department of Medical Science of Proteases, Daiya Building Lady’s Clinic, Meieki 3-15-1, Nakamura, Nagoya 450-0002, Japan

Received 1 March 2012; Accepted 26 April 2012

Academic Editor: John R. Dietz

Copyright © 2012 John W. Wright et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. R. Tigerstedt and P. G. Bergman, “Niere und Kreislauf,” Scandinavian Archives of Physiology, vol. 8, pp. 223–271, 1898.
  2. H. Goldblatt, J. Lynch, R. G. Hanzal, and W. W. Summerville, “Studies on experimental hypertension: I. The production of persistent elevation of systolic blood pressure by means of renal ischemia,” The Journal of Experimental Medicine, vol. 59, no. 3, pp. 347–379, 1934.
  3. E. Braun-Menendez, J. C. Fasciolo, L. F. Leloir, and J. M. Munoz, “The substance causing renal hypertension,” Journal of Physiology, vol. 98, no. 3, pp. 283–298, 1940.
  4. I. H. Page and O. M. Helmer, “A crystalline pressor substance (angiotonin) resulting from the reaction between renin and renin activator,” The Journal of Experimental Medicine, vol. 71, no. 1, pp. 29–42, 1940.
  5. D. F. Elliott and W. S. Peart, “Amino-acid sequence in a hypertensin,” Nature, vol. 177, no. 4507, pp. 527–528, 1956. View at Publisher · View at Google Scholar · View at Scopus
  6. L. T. Skeggs, K. E. Lentz, J. R. Kahn, N. P. Shumway, and K. R. Woods, “The amino acid sequence of hypertensin. II,” The Journal of Experimental Medicine, vol. 104, no. 2, pp. 193–197, 1956. View at Scopus
  7. F. M. Bumpus, H. Schwarz, and I. H. Page, “Synthesis and pharmacology of the octapeptide angiotonin,” Science, vol. 125, no. 3253, pp. 886–887, 1957. View at Scopus
  8. C. I. Johnston, “Biochemistry and pharmacology of the renin-angiotensin system,” Drugs, vol. 39, no. 1, pp. 21–31, 1990. View at Scopus
  9. V. T. Karamyan and R. C. Speth, “Enzymatic pathways of the brain renin-angiotensin system: unsolved problems and continuing challenges,” Regulatory Peptides, vol. 143, no. 1–3, pp. 15–27, 2007. View at Publisher · View at Google Scholar · View at Scopus
  10. R. C. Speth and V. T. Karamyan, “The significance of brain aminopeptidases in the regulation of the actions of angiotensin peptides in the brain,” Heart Failure Reviews, vol. 13, no. 3, pp. 299–309, 2008. View at Publisher · View at Google Scholar · View at Scopus
  11. C. M. Ferrario and W. B. Strawn, “Role of the renin-angiotensin-aldosterone system and proinflammatory mediators in cardiovascular disease,” American Journal of Cardiology, vol. 98, no. 1, pp. 121–128, 2006. View at Publisher · View at Google Scholar · View at Scopus
  12. T. Kokubu, E. Ueda, T. Joh, and K. Nishimura, “Purification and properties of angiotensin I-converting enzyme in human lung and its role on the metabolism of vasoactive peptides in pulmonary circulation,” Advances in Experimental Medicine and Biology, vol. 120, pp. 467–475, 1979. View at Scopus
  13. T. Unger and J. Li, “The role of the renin-angiotensin-aldosterone system in heart failure,” JRAAS, vol. 5, no. 1, supplement, pp. S7–S10, 2004. View at Scopus
  14. D. H. Rich, B. J. Moon, and S. Harbeson, “Inhibition of aminopeptidases by amastatin and bestatin derivatives. Effect of inhibitor structure on slow-binding processes,” Journal of Medicinal Chemistry, vol. 27, no. 4, pp. 417–422, 1984. View at Scopus
  15. M. Ramirez, G. Arechaga, S. Garcia, B. Sanchez, P. Lardelli, and J. M. De Gandarias, “Mn2+-activated aspartate aminopeptidase activity, subcellular localization in young and adult rat brain,” Brain Research, vol. 522, no. 1, pp. 165–167, 1990. View at Publisher · View at Google Scholar · View at Scopus
  16. S. Wilk and D. P. Healy, “Glutamyl aminopeptidase (aminopeptidase A), the BP-1/6C3 antigen,” Advances in Neuroimmunology, vol. 3, no. 3, pp. 195–207, 1993. View at Scopus
  17. E. N. Chauvel, C. Llorens-Cortes, P. Coric, S. Wilk, B. P. Roques, and M. C. Fournie- Zaluski, “Differential inhibition of aminopeptidase A and aminopeptidase N by new β-amino thiols,” Journal of Medicinal Chemistry, vol. 37, no. 18, pp. 2950–2957, 1994. View at Scopus
  18. T. Unger, E. Badoer, D. Ganten, R. E. Lang, and R. Rettig, “Brain angiotensin: pathways and pharmacology,” Circulation, vol. 77, no. 6, part 2, pp. I40–I54, 1988. View at Scopus
  19. J. M. Saavedra, “Brain and pituitary angiotensin,” Endocrine Reviews, vol. 13, no. 2, pp. 329–380, 1992. View at Publisher · View at Google Scholar · View at Scopus
  20. R. C. Speth, T. E. Brown, R. D. Barnes, and J. W. Wright, “Brain angiotensinergic activity: the state of our current knowledge,” Proceedings of the Western Pharmacology Society, vol. 46, pp. 11–15, 2003. View at Scopus
  21. T. L. Reudelhuber, “The renin-angiotensin system: peptides and enzymes beyond angiotensin II,” Current Opinion in Nephrology and Hypertension, vol. 14, no. 2, pp. 155–159, 2005. View at Scopus
  22. I. Banegas, I. Prieto, F. Vives et al., “Brain aminopeptidases and hypertension,” JRAAS, vol. 7, no. 3, pp. 129–134, 2006. View at Publisher · View at Google Scholar · View at Scopus
  23. International Union of Biochemistry, Nomenclature Committee, Enzyme Nomenclature 1984: Recommendations of the Nomenclature Committee for the International Union of Biochemistry on the Nomenclature and Classification of Enzyme-Catalyzed Reactions, Edited by E. C. Webb, International Union of Biochemistry Publications, Orlando, Fla, USA, 1984.
  24. S. Mizutani, K. Okano, and E. Hasegawa, “Aminopeptidase A in human placenta,” Biochimica et Biophysica Acta, vol. 662, no. 1, pp. 168–170, 1981. View at Scopus
  25. S. Mizutani, H. Akiyama, and O. Kurauchi, “In vitro degradation of angiotensin II (A-II) by human placental subcellular fractions, pregnancy sera and purified placental aminopeptidases,” Acta Endocrinologica, vol. 110, no. 1, pp. 135–139, 1985. View at Scopus
  26. R. Yamada, S. Mizutani, O. Kurauchi et al., “Purification and characterization of human placental aminopeptidase A,” Enzyme, vol. 40, no. 4, pp. 223–230, 1988. View at Scopus
  27. J. W. Wright and J. W. Harding, “Important roles for angiotensin III and IV in the brain renin-angiotensin system,” Brain Research Reviews, vol. 25, no. 1, pp. 96–124, 1997. View at Publisher · View at Google Scholar · View at Scopus
  28. C. M. Ferrario and M. C. Chappell, “Novel angiotensin peptides,” Cellular and Molecular Life Sciences, vol. 61, no. 21, pp. 2720–2727, 2004. View at Publisher · View at Google Scholar · View at Scopus
  29. N. E. Clarke and A. J. Turner, “Angiotensin-converting enzyme 2: the first decade,” International Journal of Hypertension, vol. 2012, Article ID 307315, 12 pages, 2012. View at Publisher · View at Google Scholar
  30. G. Vauquelin, Y. Michotte, I. Smolders et al., “Cellular targets for angiotensin II fragments: pharmacological and molecular evidence,” JRAAS, vol. 3, no. 4, pp. 195–204, 2002. View at Scopus
  31. R. Mentlein and T. Roos, “Proteases involved in the metabolism of angiotensin II, bradykinin, calcitonin gene-related peptide (CGRP), and neuropeptide Y by vascular smooth muscle cells,” Peptides, vol. 17, no. 4, pp. 709–720, 1996. View at Publisher · View at Google Scholar · View at Scopus
  32. M. De Gasparo, K. J. Catt, T. Inagami, J. W. Wright, and T. Unger, “International union of pharmacology. XXIII. The angiotensin II receptors,” Pharmacological Reviews, vol. 52, no. 3, pp. 415–472, 2000. View at Scopus
  33. R. M. Touyz and C. Berry, “Recent advances in angiotensin II signaling,” Brazilian Journal of Medical and Biological Research, vol. 35, no. 9, pp. 1001–1015, 2002. View at Scopus
  34. H. Glossmann, A. Baukal, and K. J. Catt, “Angiotensin II receptors in bovine adrenal cortex. Modification of angiotensin II binding by guanyl nucleotides,” The Journal of Biological Chemistry, vol. 249, no. 2, pp. 664–666, 1974. View at Scopus
  35. J. P. Bennett and S. H. Snyder, “Angiotensin II binding to mammalian brain membranes,” The Journal of Biological Chemistry, vol. 251, no. 23, pp. 7423–7430, 1976. View at Scopus
  36. J. W. Harding, V. I. Cook, A. V. Miller-Wing et al., “Identification of an AII (3–8) [AIV] binding site in guinea pig hippocampus,” Brain Research, vol. 583, no. 1-2, pp. 340–343, 1992. View at Scopus
  37. M. F. Jarvis, G. W. Gessner, and C. Q. Ly, “The angiotensin hexapeptide 3–8 fragment potently inhibits 125I-angiotensin II binding to non-AT1 or -AT2 recognition sites in bovine adrenal cortex,” European Journal of Pharmacology, vol. 219, no. 2, pp. 319–322, 1992. View at Scopus
  38. G. N. Swanson, J. M. Hanesworth, M. F. Sardinia et al., “Discovery of a distinct binding site for angiotensin II (3–8), a putative angiotensin IV receptor,” Regulatory Peptides, vol. 40, no. 3, pp. 409–419, 1992. View at Publisher · View at Google Scholar · View at Scopus
  39. S. G. Bernier, J. M. Bellemare, E. Escher, and G. Guillemette, “Characterization of AT4 receptor from bovine aortic endothelium with photosensitive analogues of angiotensin IV,” Biochemistry, vol. 37, no. 12, pp. 4280–4287, 1998. View at Scopus
  40. J. W. Wright, L. T. Krebs, J. W. Stobb, and J. W. Harding, “The angiotensin IV system: functional implications,” Frontiers in Neuroendocrinology, vol. 16, no. 1, pp. 23–52, 1995. View at Publisher · View at Google Scholar · View at Scopus
  41. J. W. Wright, A. J. Bechtholt, S. L. Chambers, and J. W. Harding, “Angiotensin III and IV activation of the brain AT1 receptor subtype in cardiovascular function,” Peptides, vol. 17, no. 8, pp. 1365–1371, 1996. View at Publisher · View at Google Scholar · View at Scopus
  42. N. Lochard, G. Thibault, D. W. Silversides, R. M. Touyz, and T. L. Reudelhuber, “Chronic production of angiotensin IV in the brain leads to hypertension that is reversible with an angiotensin II AT1 receptor antagonist,” Circulation Research, vol. 94, no. 11, pp. 1451–1457, 2004. View at Publisher · View at Google Scholar · View at Scopus
  43. R. Yang, I. Smolders, D. De Bundel et al., “Brain and peripheral angiotensin II type 1 receptors mediate renal vasoconstrictor and blood pressure responses to angiotensin IV in the rat,” Journal of Hypertension, vol. 26, no. 5, pp. 998–1007, 2008. View at Publisher · View at Google Scholar · View at Scopus
  44. R. Yang, T. Walther, F. Gembardt et al., “Renal vasoconstrictor and pressor responses to angiotensin IV in mice are AT1a-receptor mediated,” Journal of Hypertension, vol. 28, no. 3, pp. 487–494, 2010. View at Publisher · View at Google Scholar · View at Scopus
  45. N. M. Santiago, P. S. Guimarães, R. A. Sirvente et al., “Lifetime overproduction of circulating angiotensin-(1–7) attenuates deoxycorticosterone acetate-salt hypertension-induced cardiac dysfunction and remodeling,” Hypertension, vol. 55, no. 4, pp. 889–896, 2010. View at Publisher · View at Google Scholar · View at Scopus
  46. A. J. Ferreira, T. M. Murca, R. A. Fraga-Silva, C. H. Castro, M. K. Raizada, and R. A. S. Santos, “New cardiovascular and pulmonary therapeutic strategies based on the angiotensin-converting enzyme2/angiotensin-(1–7)/Mas receptor axis,” International Journal of Hypertension, vol. 2012, Article ID 147825, 13 pages, 2012. View at Publisher · View at Google Scholar
  47. P. P. Sayeski, M. S. Ali, D. J. Semeniuk, T. N. Doan, and K. E. Bernstein, “Angiotensin II signal transduction pathways,” Regulatory Peptides, vol. 78, no. 1–3, pp. 19–29, 1998. View at Publisher · View at Google Scholar · View at Scopus
  48. D. T. Dinh, A. G. Frauman, C. I. Johnston, and M. E. Fabiani, “Angiotensin receptors: distribution, signalling and function,” Clinical Science, vol. 100, no. 5, pp. 481–492, 2001. View at Publisher · View at Google Scholar · View at Scopus
  49. T. J. Murphy, R. W. Alexander, K. K. Griendling, M. S. Runge, and K. E. Bernstein, “Isolation of a cDNA encoding the vascular type-1 angiotensin II receptor,” Nature, vol. 351, no. 6323, pp. 233–236, 1991. View at Publisher · View at Google Scholar · View at Scopus
  50. K. Sasaki, Y. Yamano, S. Bardhan et al., “Cloning and expression of a complementary DNA encoding a bovine adrenal angiotensin II type-1 receptor,” Nature, vol. 351, no. 6323, pp. 230–233, 1991. View at Publisher · View at Google Scholar · View at Scopus
  51. K. Sandberg, H. Ji, and K. J. Catt, “Regulation of angiotensin II receptors in rat brain during dietary sodium changes,” Hypertension, vol. 23, no. 1, supplement, pp. I137–I141, 1994. View at Scopus
  52. N. Iwai and T. Inagami, “Identification of two subtypes in the rat type I angiotensin II receptor,” FEBS Letters, vol. 298, no. 2-3, pp. 257–260, 1992. View at Publisher · View at Google Scholar · View at Scopus
  53. S. S. Kakar, J. C. Sellers, D. C. Devor, L. C. Musgrove, and J. D. Neill, “Angiotensin II type-1 receptor subtype cDNAs: differential tissue expression and hormonal regulation,” Biochemical and Biophysical Research Communications, vol. 183, no. 3, pp. 1090–1096, 1992. View at Publisher · View at Google Scholar · View at Scopus
  54. H. Sasamura, L. Hein, J. E. Krieger, R. E. Pratt, B. K. Kobilka, and V. J. Dzau, “Cloning, characterization, and expression of two angiotensin receptor (AT- 1) isoforms from the mouse genome,” Biochemical and Biophysical Research Communications, vol. 185, no. 1, pp. 253–259, 1992. View at Publisher · View at Google Scholar · View at Scopus
  55. H. Konishi, S. Kuroda, Y. Inada, and Y. Fujisawa, “Novel subtype of human angiotensin II type 1 receptor: cDNA cloning and expression,” Biochemical and Biophysical Research Communications, vol. 199, no. 2, pp. 467–474, 1994. View at Publisher · View at Google Scholar · View at Scopus
  56. D. F. Guo and T. Inagami, “The genomic organization of the rat angiotensin II receptor AT(1B),” Biochimica et Biophysica Acta, vol. 1218, no. 1, pp. 91–94, 1994. View at Publisher · View at Google Scholar · View at Scopus
  57. R. C. Speth, S. M. Thompson, and S. J. Johns, “Angiotensin II receptors: structural and functional considerations,” in Current Concepts: Tissue Renin Angiotensin Systems as Local Regulators in Reproductive and Endocrine Organs, A. K. Mukhopadhyay and M. K. Raizada, Eds., pp. 169–192, Plenum Press, New York, NY, USA, 1995.
  58. J. M. Saavedra, “Emerging features of brain angiotensin receptors,” Regulatory Peptides, vol. 85, no. 1, pp. 31–45, 1999. View at Publisher · View at Google Scholar · View at Scopus
  59. W. G. Thomas and F. A. O. Mendelsohn, “Angiotensin receptors: form and function and distribution,” International Journal of Biochemistry and Cell Biology, vol. 35, no. 6, pp. 774–779, 2003. View at Publisher · View at Google Scholar · View at Scopus
  60. S. P. Bottari, V. Taylor, I. N. King, Y. Bogdal, S. Whitebread, and M. De Gasparo, “Angiotensin II AT2 receptors do not interact with guanine nucleotide binding proteins,” European Journal of Pharmacology, vol. 207, no. 2, pp. 157–163, 1991. View at Publisher · View at Google Scholar · View at Scopus
  61. Y. Kambayashi, S. Bardhan, K. Takahashi et al., “Molecular cloning of a novel angiotensin II receptor isoform involved in phosphotyrosine phosphatase inhibition,” The Journal of Biological Chemistry, vol. 268, no. 33, pp. 24543–24546, 1993. View at Scopus
  62. M. Mukoyama, M. Nakajima, M. Horiuchi, H. Sasamura, R. E. Pratt, and V. J. Dzau, “Expression cloning of type 2 angiotensin II receptor reveals a unique class of seven-transmembrane receptors,” The Journal of Biological Chemistry, vol. 268, no. 33, pp. 24539–24542, 1993. View at Scopus
  63. D. Young, G. Waitches, and C. Birchmeier, “Isolation and characterization of a new cellular oncogene encoding a protein with multiple potential transmembrane domains,” Cell, vol. 45, no. 5, pp. 711–719, 1986. View at Scopus
  64. X. Xu, A. B. Quiambao, L. Roveri et al., “Degeneration of cone photoreceptors induced by expression of the Mas1 protooncogene,” Experimental Neurology, vol. 163, no. 1, pp. 207–219, 2000. View at Publisher · View at Google Scholar · View at Scopus
  65. N. Alenina, P. Xu, B. Rentzsch, E. L. Patkin, and M. Bader, “Genetically altered animal models for Mas and angiotensin-(1–7),” Experimental Physiology, vol. 93, no. 5, pp. 528–537, 2008. View at Publisher · View at Google Scholar · View at Scopus
  66. D. Young, K. O'Neill, T. Jessell, and M. Wigler, “Characterization of the rat mas oncogene and its high-level expression in the hippocampus and cerebral cortex of rat brain,” Proceedings of the National Academy of Sciences of the United States of America, vol. 85, no. 14, pp. 5339–5342, 1988. View at Scopus
  67. M. Bader, “Expression of the mouse and rat mas proto-oncogene in the brain and peripheral tissues,” FEBS Letters, vol. 357, no. 1, pp. 27–32, 1995. View at Publisher · View at Google Scholar · View at Scopus
  68. S. V. B. Pinheiro, A. C. Simões E Silva, W. O. Sampaio et al., “Nonpeptide AVE 0991 is an angiotensin-(1–7) receptor mas agonist in the mouse kidney,” Hypertension, vol. 44, no. 4, pp. 490–496, 2004. View at Publisher · View at Google Scholar · View at Scopus
  69. A. J. Ferreira, T. M. Murca, R. A. Fraga-Silva, C. H. Castro, M. K. Raizada, and R. A. S. Santos, “New cardiovascular and pulmonary therapeutic strategies based on the angiotensin-converting enzyme2/angiotensin-(1–7)/Mas receptor axis,” International Journal of Hypertension, vol. 2012, Article ID 147825, 13 pages, 2012. View at Publisher · View at Google Scholar
  70. P. Xu, S. Sriramula, and E. Lazartigues, “ACE2/ANG-(1–7)/Mas pathway in the brain: the axis of good,” American Journal of Physiology, vol. 300, no. 4, pp. R804–R817, 2011. View at Publisher · View at Google Scholar · View at Scopus
  71. J. L. Grobe, A. P. Mecca, M. Lingis et al., “Prevention of angiotensin II-induced cardiac remodeling by angiotensin-(1–7),” American Journal of Physiology, vol. 292, no. 2, pp. H736–H742, 2007. View at Publisher · View at Google Scholar · View at Scopus
  72. A. J. Ferreira, C. H. Castro, S. Guatimosim et al., “Attenuation of isoproterenol-induced cardiac fibrosis in transgenic rats harboring an angiotensin-(1–7)-producing fusion protein in the heart,” Therapeutic Advances in Cardiovascular Disease, vol. 4, no. 2, pp. 83–96, 2010. View at Publisher · View at Google Scholar · View at Scopus
  73. N. M. Santiago, P. S. Guimarães, R. A. Sirvente et al., “Lifetime overproduction of circulating angiotensin-(1–7) attenuates deoxycorticosterone acetate-salt hypertension-induced cardiac dysfunction and remodeling,” Hypertension, vol. 55, no. 4, pp. 889–896, 2010. View at Publisher · View at Google Scholar · View at Scopus
  74. C. Vickers, P. Hales, V. Kaushik et al., “Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase,” The Journal of Biological Chemistry, vol. 277, no. 17, pp. 14838–14843, 2002. View at Publisher · View at Google Scholar · View at Scopus
  75. M. Donoghue, F. Hsieh, E. Baronas et al., “A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1–9,” Circulation Research, vol. 87, no. 5, pp. E1–E9, 2000. View at Scopus
  76. J. A. Hernández Prada, A. J. Ferreira, M. J. Katovich et al., “Structure-based identification of small-molecule angiotensin-converting enzyme 2 activators as novel antihypertensive agents,” Hypertension, vol. 51, no. 5, pp. 1312–1317, 2008. View at Publisher · View at Google Scholar · View at Scopus
  77. S. Q. Savergnini, M. Beiman, R. Q. Lautner et al., “Vascular relaxation, antihypertensive effect, and cardioprotection of a novel peptide agonist of the mas receptor,” Hypertension, vol. 56, no. 1, pp. 112–120, 2010. View at Publisher · View at Google Scholar · View at Scopus
  78. A. J. Barret, N. D. Rawlings, and J. F. Woessner, Eds., Handbook of Proteolytic Enzymes, Academic Press, London, UK, 1998.
  79. A. L. Albiston, S. G. McDowall, D. Matsacos et al., “Evidence that the angiotensin IV (AT4) receptor is the enzyme insulin regulated aminopeptidase,” The Journal of Biological Chemistry, vol. 276, no. 52, pp. 48623–48626, 2001. View at Publisher · View at Google Scholar · View at Scopus
  80. M. I. Phillips, “Functions of angiotensin in the central nervous system,” Annual Review of Physiology, vol. 49, pp. 413–435, 1987. View at Scopus
  81. J. W. Wright and J. W. Harding, “Regulatory role of brain angiotensins in the control of physiological and behavioral responses,” Brain Research Reviews, vol. 17, no. 3, pp. 227–262, 1992. View at Publisher · View at Google Scholar · View at Scopus
  82. D. Felix and W. Schlegel, “Angiotensin receptive neurones in the subfornical organ. Structure-activity relations,” Brain Research, vol. 149, no. 1, pp. 107–116, 1978. View at Publisher · View at Google Scholar · View at Scopus
  83. J. W. Harding and D. Felix, “Angiotensin-sensitive neurons in the rat paraventricular nucleus: relative potencies of angiotensin II and angiotensin III,” Brain Research, vol. 410, no. 1, pp. 130–134, 1987. View at Scopus
  84. J. W. Harding and D. Felix, “The effects of the aminopeptidase inhibitors amastatin and bestatin on angiotensin-evoked neuronal activity in rat brain,” Brain Research, vol. 424, no. 2, pp. 299–304, 1987. View at Scopus
  85. J. W. Harding, L. L. Jensen, J. M. Hanesworth, K. A. Roberts, T. A. Page, and J. W. Wright, “Release of angiotensins in paraventricular nucleus of rat in response to physiological and chemical stimuli,” American Journal of Physiology, vol. 262, no. 1, pp. F17–F23, 1992. View at Scopus
  86. L. L. Jensen, J. W. Harding, and J. W. Wright, “Increased blood pressure induced by central application of aminopeptidase inhibitors is angiotensinergic-dependent in normotensive and hypertensive rat strains,” Brain Research, vol. 490, no. 1, pp. 48–55, 1989. View at Scopus
  87. J. W. Wright, M. J. Sullivan, and C. R. Bredl, “Delayed cerebroventricular metabolism of 125I-angiotensins in the spontaneously hypertensive rat,” Journal of Neurochemistry, vol. 49, no. 2, pp. 651–654, 1987. View at Scopus
  88. J. W. Wright, L. L. Jensen, L. L. Cushing, and J. W. Harding, “Leucine aminopeptidase M-induced reductions in blood pressure in spontaneously hypertensive rats,” Hypertension, vol. 13, no. 6, pp. 910–915, 1989. View at Scopus
  89. J. W. Wright, S. Mizutani, C. E. Murray, H. Z. Amir, and J. W. Harding, “Aminopeptidase-induced elevations and reductions in blood pressure in the spontaneously hypertensive rat,” Journal of Hypertension, vol. 8, no. 10, pp. 969–974, 1990. View at Scopus
  90. J. W. Wright, K. A. Roberts, V. I. Cook, C. E. Murray, M. F. Sardinia, and J. W. Harding, “Intracerebroventricularly infused [D-Arg1]angiotensin III, is superior to [D-Asp1]angiotensin II, as a pressor agent in rats,” Brain Research, vol. 514, no. 1, pp. 5–10, 1990. View at Publisher · View at Google Scholar · View at Scopus
  91. J. W. Wright, E. Tamura-Myers, W. L. Wilson et al., “Conversion of brain angiotensin II to angiotensin III is critical for pressor response in rats,” American Journal of Physiology, vol. 284, no. 3, pp. R725–R733, 2003. View at Scopus
  92. A. Stanton, “Potential of renin inhibition in cardiovascular disease,” JRAAS, vol. 4, no. 1, pp. 6–10, 2003. View at Scopus
  93. L. S. Zisman, W. T. Abraham, G. E. Meixell et al., “Angiotensin II formation in the intact human heart. Predominance of the angiotensin-converting enzyme pathway,” The Journal of Clinical Investigation, vol. 96, no. 3, pp. 1490–1498, 1995. View at Scopus
  94. I. J. Dell’Italia and A. Sabri, “Activation of the renin-angiotensin system in hypertrophy and heart failure,” in Heart Failure, D. L. Mann, Ed., Saunders, Philadelphia, Pa, USA, 2004.
  95. Y. H. Liu, X. P. Yang, V. G. Sharov et al., “Effects of angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor antagonists in rats with heart failure: role of kinins and angiotensin II type 2 receptors,” The Journal of Clinical Investigation, vol. 99, no. 8, pp. 1926–1935, 1997. View at Scopus
  96. K. F. Adams Jr., “Pathophysiologic role of the renin-angiotensin-aldosterone and sympathetic nervous systems in heart failure,” American Journal of Health-System Pharmacy, vol. 61, supplement 2, pp. S4–S13, 2004. View at Scopus
  97. C. G. Brilla, R. Pick, L. B. Tan, J. S. Janicki, and K. T. Weber, “Remodeling of the rat right and left ventricles in experimental hypertension,” Circulation Research, vol. 67, no. 6, pp. 1355–1364, 1990. View at Scopus
  98. H. N. Sabbah, P. D. Stein, T. Kono et al., “A canine model of chronic heart failure produced by multiple sequential coronary microembolizations,” American Journal of Physiology, vol. 260, no. 4, pp. H1379–H1384, 1991. View at Scopus
  99. R. S. McKelvie, S. Yusuf, D. Pericak et al., “Comparison of candesartan, enalapril, and their combination in congestive heart failure: randomized evaluation of strategies for left ventricular dysfunction (RESOLVD) pilot study: the RESOLVD pilot study investigators,” Circulation, vol. 100, no. 10, pp. 1056–1064, 1999. View at Scopus
  100. B. Pitt, N. Reichek, R. Willenbrock et al., “Effects of eplerenone, enalapril, and eplerenone/enalapril in patients with essential hypertension and left ventricular hypertrophy: the 4E-Left Ventricular Hypertrophy Study,” Circulation, vol. 108, no. 15, pp. 1831–1838, 2003. View at Publisher · View at Google Scholar · View at Scopus
  101. W. Hayashida, J. Donckier, H. Van Mechelen, A. A. Charlier, and H. Pouleur, “Diastolic properties in canine hypertensive left ventricular hypertrophy: effects of angiotensin converting enzyme inhibition and angiotensin II type-1 receptor blockade,” Cardiovascular Research, vol. 33, no. 1, pp. 54–62, 1997. View at Publisher · View at Google Scholar · View at Scopus
  102. K. Wachtell, J. N. Bella, J. Rokkedal et al., “Change in diastolic left ventricular filling after one year of antihypertensive treatment: the losartan intervention for endpoint reduction in hypertension (LIFE) study,” Circulation, vol. 105, no. 9, pp. 1071–1076, 2002. View at Publisher · View at Google Scholar · View at Scopus
  103. J. Díez, R. Querejeta, B. López, A. González, M. Larman, and J. L. Martínez Ubago, “Losartan-dependent regression of myocardial fibrosis is associated with reduction of left ventricular chamber stiffness in hypertensive patients,” Circulation, vol. 105, no. 21, pp. 2512–2517, 2002. View at Publisher · View at Google Scholar · View at Scopus
  104. S. Yusuf, M. A. Pfeffer, K. Swedberg et al., “Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-preserved trial,” The Lancet, vol. 362, no. 9386, pp. 777–781, 2003. View at Publisher · View at Google Scholar · View at Scopus
  105. A. Reaux, M. C. Fournie-Zaluski, C. David et al., “Aminopeptidase A inhibitors as potential central antihypertensive agents,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 23, pp. 13415–13420, 1999. View at Publisher · View at Google Scholar · View at Scopus
  106. J. J. Morton, J. Casals-Stenzel, and A. F. Lever, “Inhibitors of the renin-angiotensin system in experimental hypertension, with a note on the measurement of angiotensin I, II and III during infusion of converting-enzyme inhibitor,” British Journal of Clinical Pharmacology, vol. 7, supplement 2, pp. 233S–241S, 1979. View at Scopus
  107. M. C. Fournie-Zaluski, C. Fassot, B. Valentin et al., “Brain renin-angiotensin system blockade by systemically active aminopeptidase A inhibitors: a potential treatment of salt-dependent hypertension,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 20, pp. 7775–7780, 2004. View at Publisher · View at Google Scholar · View at Scopus
  108. S. Zini, M. C. Fournie-Zaluski, E. Chauvel, B. P. Roques, P. Corvol, and C. Llorens-Cortes, “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,” Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 21, pp. 11968–11973, 1996. View at Publisher · View at Google Scholar · View at Scopus
  109. C. M. Ferrario, “Angiotensin-converting enzyme 2 and angiotensin-(1–7): an evolving story in cardiovascular regulation,” Hypertension, vol. 47, no. 3, pp. 515–521, 2006. View at Publisher · View at Google Scholar · View at Scopus
  110. R. J. Kokje, W. L. Wilson, T. E. Brown, V. T. Karamyan, J. W. Wright, and R. C. Speth, “Central pressor actions of aminopeptidase-resistant angiotensin II analogs: challenging the angiotensin III hypothesis,” Hypertension, vol. 49, no. 6, pp. 1328–1335, 2007. View at Publisher · View at Google Scholar · View at Scopus
  111. A. Reaux, M. C. Fournie-Zaluski, and C. Llorens-Cortes, “Angiotensin III: a central regulator of vasopressin release and blood pressure,” Trends in Endocrinology and Metabolism, vol. 12, no. 4, pp. 157–162, 2001. View at Scopus
  112. S. Zini, Y. Demassey, M. C. Fournié-Zaluski et al., “Inhibition of vasopressinergic neurons by central injection of a specific aminopeptidase A inhibitor,” NeuroReport, vol. 9, no. 5, pp. 825–828, 1998. View at Scopus
  113. A. Réaux, N. De Mota, S. Zini et al., “PC18, a specific aminopeptidase N inhibitor, induces vasopressin release by increasing the half-life of brain Angiotensin III,” Neuroendocrinology, vol. 69, no. 5, pp. 370–376, 1999. View at Publisher · View at Google Scholar · View at Scopus
  114. L. Bodineau, A. Frugière, Y. Marc et al., “Orally active aminopeptidase A inhibitors reduce blood pressure: a new strategy for treating hypertension,” Hypertension, vol. 51, no. 5, pp. 1318–1325, 2008. View at Publisher · View at Google Scholar · View at Scopus
  115. L. Bodineau, A. Frugière, Y. Marc, C. Claperon, and C. Llorens-Cortes, “Aminopeptidase A inhibitors as centrally acting antihypertensive agents,” Heart Failure Reviews, vol. 13, no. 3, pp. 311–319, 2008. View at Publisher · View at Google Scholar · View at Scopus
  116. L. Song, S. Wilk, and D. P. Healy, “Aminopeptidase A antiserum inhibits intracerebroventricular angiotensin II-induced dipsogenic and pressor responses,” Brain Research, vol. 744, no. 1, pp. 1–6, 1997. View at Publisher · View at Google Scholar · View at Scopus
  117. Y. Marc and C. Llorens-Cortes, “The role of the brain renin-angiotensin system in hypertension: implications for new treatment,” Progress in Neurobiology, vol. 95, no. 2, pp. 89–103, 2011. View at Publisher · View at Google Scholar
  118. S. Ahmad and P. E. Ward, “Role of aminopeptidase activity in the regulation of the pressor activity of circulating angiotensins,” Journal of Pharmacology and Experimental Therapeutics, vol. 252, no. 2, pp. 643–650, 1990. View at Scopus
  119. J. W. Harding, M. S. Yoshida, and R. P. Dilts, “Cerebroventricular and intravascular metabolism of 125I-angiotensins in rat,” Journal of Neurochemistry, vol. 46, no. 4, pp. 1292–1297, 1986. View at Scopus
  120. D. H. Rich, B. J. Moon, and S. Harbeson, “Inhibition of aminopeptidases by amastatin and bestatin derivatives. Effect of inhibitor structure on slow-binding processes,” Journal of Medicinal Chemistry, vol. 27, no. 4, pp. 417–422, 1984. View at Scopus
  121. M. Ramirez, G. Arechaga, S. Garcia, B. Sanchez, P. Lardelli, and J. M. De Gandarias, “Mn2+-activated aspartate aminopeptidase activity, subcellular localization in young and adult rat brain,” Brain Research, vol. 522, no. 1, pp. 165–167, 1990. View at Publisher · View at Google Scholar · View at Scopus
  122. R. Ardaillou, “Active fragments of angiotensin II: enzymatic pathways of synthesis and biological effects,” Current Opinion in Nephrology and Hypertension, vol. 6, no. 1, pp. 28–34, 1997. View at Publisher · View at Google Scholar · View at Scopus
  123. M. Ramírez, I. Prieto, F. Alba, F. Vives, I. Banegas, and M. de Gasparo, “Role of central and peripheral aminopeptidase activities in the control of blood pressure: a working hypothesis,” Heart Failure Reviews, vol. 13, no. 3, pp. 339–353, 2008. View at Publisher · View at Google Scholar · View at Scopus
  124. S. Bernardi, W. C. Burns, B. Toffoli, et al., “Angiotensin converting enzyme 2 regulates renal atrial natriuretic peptide through angiotensin-(1–7),” Clinical Science, vol. 123, no. 1, pp. 29–37, 2012.
  125. J. W. Wright and J. W. Harding, “Brain renin-angiotensin-A new look at an old system,” Progress in Neurobiology, vol. 95, no. 1, pp. 49–67, 2011. View at Publisher · View at Google Scholar · View at Scopus
  126. Y. Goto, A. Hattori, Y. Ishii, and M. Tsujimoto, “Reduced activity of the hypertension-associated Lys528Arg mutant of human adipocyte-derived leucine aminopeptidase (A-LAP)/ER-aminopeptidase-1,” FEBS Letters, vol. 580, no. 7, pp. 1833–1838, 2006. View at Publisher · View at Google Scholar · View at Scopus
  127. M. Ishii, A. Hattori, Y. Numaguchi et al., “The effect of recombinant aminopeptidase A on hypertension in spontaneously hypertensive rats: its effect in comparison with candesartan,” Hormone and Metabolic Research, vol. 40, no. 12, pp. 887–891, 2008. View at Publisher · View at Google Scholar · View at Scopus
  128. D. P. Healy and L. Song, “Kidney aminopeptidase A and hypertension, part I: spontaneously hypertensive rats,” Hypertension, vol. 33, no. 2, pp. 740–745, 1999. View at Scopus
  129. W. Raasch, O. Jöhren, S. Schwartz, A. Gieselberg, and P. Dominiak, “Combined blockade of AT1-receptors and ACE synergistically potentiates antihypertensive effects in SHR,” Journal of Hypertension, vol. 22, no. 3, pp. 611–618, 2004. View at Publisher · View at Google Scholar · View at Scopus
  130. S. Mizutani, K. Okano, and E. Hasegawa, “Human placental leucine aminopeptidase (P-LAP) as a hypotensive agent,” Experientia, vol. 38, no. 7, pp. 821–822, 1982. View at Scopus
  131. S. Mizutani, M. Furuhashi, H. Imaizumi, Y. Ito, O. Kurauchi, and Y. Tomoda, “Effects of human placental aminopeptidases in spontaneously hypertensive rats,” Medicinal Science Research, vol. 15, no. 1, pp. 1203–1204, 1987.
  132. J. W. Wright, M. J. Sullivan, and J. W. Harding, “Dysfunction of central angiotensinergic aminopeptidase activity in spontaneously hypertensive rats,” Neuroscience Letters, vol. 61, no. 3, pp. 351–356, 1985. View at Scopus
  133. Y. Nakashima, Y. Ohno, A. Itakura et al., “Possible involvement of aminopeptidase A in hypertension in spontaneously hypertensive rats (SHRs) and change of refractoriness in response to angiotensin II in pregnant SHRs,” Journal of Hypertension, vol. 20, no. 11, pp. 2233–2238, 2002. View at Publisher · View at Google Scholar · View at Scopus
  134. S. Mizutani, J. Wright, and H. Kobayashi, “A new approach regarding the treatment of preeclampsia and preterm labor,” Life Sciences, vol. 88, no. 1-2, pp. 17–23, 2011. View at Publisher · View at Google Scholar · View at Scopus
  135. H. Kobayashi, S. Mizutani, and J. W. Wright, “Placental leucine aminopeptidase- and aminopeptidase A-deficient mice offer insight concerning the mechanisms underlying preterm labor and preeclampsia,” Journal of Biomedicine and Biotechnology, vol. 2011, Article ID 286947, 12 pages, 2011. View at Publisher · View at Google Scholar · View at Scopus
  136. R. S. Danziger, “Aminopeptidase N in arterial hypertension,” Heart Failure Reviews, vol. 13, no. 3, pp. 293–298, 2008. View at Publisher · View at Google Scholar · View at Scopus
  137. C. Lerche, L. K. Vogel, L. H. Shapiro, O. Norén, and H. Sjöström, “Human aminopeptidase N is encoded by 20 exons,” Mammalian Genome, vol. 7, no. 9, pp. 712–713, 1996. View at Scopus
  138. N. Yamamoto, J. Nakayama, K. Yamakawa-Kobayashi, H. Hamaguchi, R. Miyazaki, and T. Arinami, “Identification of 33 polymorphisms in the adipocyte-derived leucine aminopeptidase (ALAP) gene and possible association with hypertension,” Human Mutation, vol. 19, no. 3, pp. 251–257, 2002. View at Publisher · View at Google Scholar · View at Scopus
  139. J. S. Williams, A. Raji, G. H. Williams, and P. R. Conlin, “Nonmodulating hypertension is associated with insulin resistance and the Lys528Arg variant human adipocyte-derived leucine aminopeptidase,” Hypertension, vol. 48, no. 4, article e33, 2006.
  140. K. Sri Krishna, M. G. Kirubakaran, A. P. Pandey, and A. S. Kanagasabapathy, “Urinary N-acetyl-β-d-glucosaminidase and aminopeptidase N in the diagnosis of graft rejection after live donor renal transplantation,” Clinica Chimica Acta, vol. 150, no. 2, pp. 69–85, 1985. View at Scopus
  141. Y. Kitamura, M. Watanabe, S. Komatsubara, and Y. Sakata, “Urinary excretion of glycine.prolile dipeptidile aminopeptidase, N-acetyl-beta-D-glucosaminidase, alanine aminopeptidase and low molecular protein in patients with renal cell carcinoma,” Acta Urologica Japonica, vol. 36, no. 5, pp. 535–539, 1990. View at Scopus
  142. S. H. Padia, N. L. Howell, B. A. Kemp, M. C. Fournie-Zaluski, B. P. Roques, and R. M. Carey, “Intrarenal aminopeptidase N inhibition restores defective angiontesin II type 2-mediated natriuresis in spontaneously hypertensive rats,” Hypertension, vol. 55, no. 2, pp. 474–480, 2010. View at Publisher · View at Google Scholar · View at Scopus
  143. S. H. Padia, B. A. Kemp, N. L. Howell, J. J. Gildea, S. R. Keller, and R. M. Carey, “Intrarenal angiotensin III infusion induces natriuresis and angiotensin type 2 receptor translocation in Wistar-Kyoto but not in spontaneously hypertensive rats,” Hypertension, vol. 53, no. 2, pp. 338–343, 2009. View at Publisher · View at Google Scholar · View at Scopus
  144. B. Bauvois and D. Dauzonne, “Aminopeptidase-N/CD13 (EC 3.4.11.2) inhibitors: chemistry, biological evaluations, and therapeutic prospects,” Medicinal Research Reviews, vol. 26, no. 1, pp. 88–130, 2006. View at Publisher · View at Google Scholar · View at Scopus
  145. R. Düsing, “Optimizing blood pressure control through the use of fixed combinations,” Vascular Health and Risk Management, vol. 6, pp. 321–325, 2010. View at Scopus
  146. P. M. Kearney, M. Whelton, K. Reynolds, P. Muntner, P. K. Whelton, and J. He, “Global burden of hypertension: analysis of worldwide data,” The Lancet, vol. 365, no. 9455, pp. 217–223, 2005. View at Publisher · View at Google Scholar · View at Scopus
  147. K. Wolf-Maier, R. S. Cooper, H. Kramer et al., “Hypertension treatment and control in five European countries, Canada, and the United States,” Hypertension, vol. 43, no. 1, pp. 10–17, 2004. View at Publisher · View at Google Scholar · View at Scopus