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Measurement of patient compliance.

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Abstract

Recent developments in our knowledge of the renin‐angiotensin system (RAS) necessitate an update of the classical view on this system. These developments pertain to the pathways leading to formation of angiotensin II and other active metabolites, their receptors, biological functions and the presence of renin‐angiotensin systems in tissues. The implications of the above new developments for the current interest in tissue renin‐angiotensin systems as potential targets for drug therapy in cardiovascular disease are discussed in this review.

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References

  1. Leonetti G, Cuspidi C. Choosing the right ACE inhibitor. Drugs 1995;49:516–35.

    Google Scholar 

  2. Johnston CI. Renin-angiotensin system: a dual tissue and hormonal system for cardiovascular control. J Hypertens 1992;10(Suppl. 7):S13–26.

    Google Scholar 

  3. Boucher R, Asselin JH, Genest J. A new enzyme leading to direct formation of angiotensin II. Circ Res 1974;34(Suppl. 1):I203–9.

    Google Scholar 

  4. Wintroub B, Klickstein LB, Dzau VJ, Watt KWK. Granulocyteangiotensin system: identification of angiotensinogen as substrate of leucocyte cathepsin G. Biochemistry 1984;23:227–32.

    Google Scholar 

  5. Tang SS, Loscalzo J, Dzau VJ. Tissue plasminogen activator actvates renin angiotensin in vitro. J Vasc Med Biol 1989;1:67–74.

    Google Scholar 

  6. Boer PH, Ruzicka M, Lear W, Harmsen E, Rosenthal J, Leenen FH. Stretch-mediated activation of cardiac renin gene. Am J Physiol 1994;267:H1630–1636.

    Google Scholar 

  7. Dzau VJ, Sasamura H, Hein L. Circulating versus local reninangiotensin system in cardiovascular homeostasis. J Hypertens 1993;11(Suppl. 3):S13–8.

    Google Scholar 

  8. Urata H, Healey B, Stewart RW, Bumpus FM, Hussain A. Angiotensin II-forming pathways in normal and failing human hearts. Circ Res 1990;66:883–90.

    Google Scholar 

  9. Urata H, Strobel F, Ganten D. Widerspread tissue distribution of human chymase. J Hypertens 1994;12(Suppl. 9):S17–22.

    Google Scholar 

  10. Moriguchi A, Tallant A, Matsumura K, et al. Opposing actions of angiotensin-(1-7) and angiotensin II in the brain of transgenic hypertensive rats. Hypertension 1995;25:1260–5.

    Google Scholar 

  11. Abdelrahman A, Pang CCY. Competitive antagonism of pressor responses to angiotensin II and angiotensin III by the angiotensin II-1 receptor ligand losartan. Can J Physiol Pharmacol 1992;70:716–19.

    Google Scholar 

  12. Brown NJ, Vaughan DE. The renin-angiotensin and fibrinolytic systems. Co-conspirators in the pathogenesis of ischemic cardiovascular disease. Trends Cardiovasc Med 1996;6:239–43.

    Google Scholar 

  13. Goodfriend TL. Angiotensins: a family that grows from within. Hypertension 1991;17:139–40.

    Google Scholar 

  14. Douglas JG. Angiotensin II receptor subtypes of the kidney cortex. Am J Physiol 1987;253:F1–7.

    Google Scholar 

  15. Bumpus FM, Catt KJ, Chiu AT, et al. Nomenclature for angiotensin receptors. Hypertension 1991;17:720–3.

    Google Scholar 

  16. Murphy TJ, Alexander RW, Griendling KK, Runge MS, Bernstein KE. Isolation of a cDNA encoding the vascular type-1 angiotensin II receptor. Nature 1991;351:233–6.

    Google Scholar 

  17. 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;351:230–2.

    Google Scholar 

  18. Mukoyama M, Nakajima M, Horiuchi M, Sasamura H, Pratt RE, Dzau VJ. Expression cloning of type 2 angiotensin II receptor reveals a unique class of seven-transmembrane receptors. J Biol Chem 1993;268:24539–42.

    Google Scholar 

  19. Kambayashi Y, Bardhan S, Takahashi K, et al. Molecular cloning of a novel angiotensin II receptor isoform involved in phophotyrosine phosphatase inhibition. J Biol Chem 1993;268:24543–6.

    Google Scholar 

  20. Inagami T, Mizukoshi M, Guo D-F. Angiotesnin II receptor: molecular cloning, functions and regulation. In: Saavedra JM and Timmermans PBMWM, eds. Angiotesnin receptors. New York: Plenum Press, 1994:1–17.

    Google Scholar 

  21. Inagami T, Guo D-F, Kitami Y. Molecular biology of angiotensin II receptors: an overview. J Hypertens 1994;12(Suppl. 10):83–94.

    Google Scholar 

  22. Zhang J, Pratt RE. The AT-2 receptor selectively associates with G-iα2 and G-iα3 in the rat fetus. J Biol Chem 1996;271:15026–33.

    Google Scholar 

  23. Bottari SP, King IN, Reichlin S, Dahlstroem I, Lydon N, De Gasparo M. The angiotensin AT2 receptor stimulates protein tyrosine phosphatase activity and mediates inhibition of particulate guanylate cyclase. Biochem Biophys Res Comm 1992;1:206–11.

    Google Scholar 

  24. Nakajima M, Hutchinson HG, Fujinaga M, et al. The angiotensin II type 2 (AT-2) receptor antagonizes the growth effects of the AT-1 receptopr: gain-of-function study using gene transfer. Proc Natl Acad Sci USA 1995;92:10663–7.

    Google Scholar 

  25. Tsuzuki S, Matoba T, Eguchi S, Inagami T. Angiotensin II type 2 receptor inhibits cell proliferation and activates tyrosine phosphatase. Hypertension 1996;28:916–18.

    Google Scholar 

  26. Ji H, Sandberg K, Khang Y, Catt KJ. Molecular cloning, sequencing and functional expression of an amphibian angiotensin II receptor. Biochem Biophys Res Comm 1993;194:756–62.

    Google Scholar 

  27. Sandberg K, Ji H, Clark AJL, Shapira H, Catt KJ. Cloning and expression of a novel angiotensin II receptor subtype. J Biol Chem 1992;267:9455–8.

    Google Scholar 

  28. Murphy TJ, Nakamura Y, Takeuchi K, Alexander RW. A cloned angiotensin receptor isoform from the turkey adrenal gland is pharmacologically distinct from mammalian angiotensin receptors. Mol Pharmacol 1993;44:1–7.

    Google Scholar 

  29. LeNoble FAC, Schreurs NHJS, Van Straaten HWM, et al. Evidence for a novel angiotensin II receptor involved in angiogenesis in chick embryo chorioallantoic membrane. Am J Physiol 1993;264:R460–5.

    Google Scholar 

  30. Ahmed A, Li XF, Shams M, et al. Localization of the angiotensin II and its receptor subtype expression in human endometrium and identification of a novel high-affinity angiotensin II binding site. JClinInvest 1995;96:848–57.

    Google Scholar 

  31. Neuss M, Regitz-Zagrosek V, Hildebrandt A, Fleck E. Human cardiac fibroblasts express an angiotensin receptor with unusual binding characteristics which is coupled to cellular proliferation. Biochem Biophys Res Comm 1994;204:1334–9.

    Google Scholar 

  32. Hanesworth JM, Sardinia MF, Krebs LT, Hall KL, Harding JW. Elucidation of a specific binding site for angiotensin II(3-8), angiotensin IV, in mammalian heart membranes. J Pharmacol Exp Ther 1993;266:1036–42.

    Google Scholar 

  33. Hall KL, Venkateswaran S, Hanesworth JM, Schelling ME, Harding JW. Characterization of a functional angiotensin IV receptor on coronary microvascular endothelial cells. Regul Pept 1995;58:107–15.

    Google Scholar 

  34. Regitz-Zagrosek V, Friedel N, Heymann A, et al. Regulation, chamber localization, and subtype distribution of angiotensin II receptors in human hearts. Circulation 1995;91:1461–71.

    Google Scholar 

  35. Timmermans PBMWM, Wong PC, Chiu AT, et al. Angiotensin II receptors and angiotensin II receptor antagonists. Pharmacol Rev 1993;45:206–51.

    Google Scholar 

  36. Meggs LG, Coupet J, Huang H, et al. Regulation of angiotensin II receptors on ventricular myocytes after myocardial infarction in rats. Circ Res 1993;72:1149–62.

    Google Scholar 

  37. Suzuki J, Matsubara H, Urakami M, Inada M. Rat angiotensin II receptor mRNA regulation and subtype expression in myocardial growth and hypertrophy. Circ Res 1993;73:439–47.

    Google Scholar 

  38. de Gasparo M, Rogg H, Brink M, et al. Angiotensin II receptor subtypes and cardiac function. Europ Heart J 1994;15(Suppl. D):98–103.

    Google Scholar 

  39. Rogg H, de Gasparo M, Graedel E, et al. Angiotensin II-receptor subtypes in human atria and evidence for alterations in patients with cardiac dysfunction. Europ Heart J 1996;17:1112–20.

    Google Scholar 

  40. Neyses L, Nouskas J, Luyken J, et al. Induction of immediate-early genes by angiotensin II and endothelin-1 in adult cardiomyocytes. J Hypertens 1993;11:927–34.

    Google Scholar 

  41. Booz GW, Baker KM. Role of type 1 and type 2 angiotensin receptors in angiotensin II induced cardiomyocyte hypertrophy. Hypertension 1996;28:635–40.

    Google Scholar 

  42. Schorb W, Booz GW, Dostal DE, Conrad KM, Chang KC, Baker KM. Angiotensin II is mitogenic in neonatal rat cardiac fibroblasts. Circ Res 1993;72:1245–54.

    Google Scholar 

  43. Berk BC, Vekshtein V, Gordon HM, Tsuda T. Angiotensin II-Stimulated Protein Synthesis in Cultured Vascular Smooth Muscle Cells. Hypertension 1989;13:305–14.

    Google Scholar 

  44. Bunkenburg B, van Amelsvoort T, Rogg H, Wood JM. Receptor-mediated effects of angiotensin II on growth of vascular smooth muscle cells from spontaneously hypertensive rats. Hypertension 1992;20:746–5.

    Google Scholar 

  45. Holycross BJ, Peach MJ, Owens GK. Angiotensin II stimulates increased protein synthesis, not increased DNA synthesis, in intact rat aortic segments, in vitro. J Vasc Res 1993;30:80–6.

    Google Scholar 

  46. Wolf G, Ziyadeh FN, Zahner G, Stahl RAK. Angiotensin II is mitogenic for cultured rat glomerular endothelial cells. Hypertension 1996;27:897–905.

    Google Scholar 

  47. Stoll M, Meffert S, Stroth U, Unger T. Growth or antigrowth: angiotensin and the endothelium. J Hypertens 1995;13:1529–34.

    Google Scholar 

  48. Bernstein KE, Marrero MB. The importance of tyrosine phosphorylation in angiotensin II signaling. Trends Cardiovasc Med 1996;6:179–87.

    Google Scholar 

  49. Rajagopalan S, Kurz S, Münzel T, et al. Angiotensin II mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. Contribution to alterations of vasomotor tone. J Clin Invest 1996;97:1916–23.

    Google Scholar 

  50. Rajagopalan S, Harrison DG. Reversing endothelial dysfunction with ACE inhibitors. A new trend? Circulation 1996;94:240–3.

    Google Scholar 

  51. Tan LB, Jalil JE, Pick R, Janicki JS, Weber KT. Cardiomyocyte necrosis induced by angiotensin II. Circ Res 1991;69:1185–95.

    Google Scholar 

  52. Pollman M, Yamada T, Horiuchi M, Gibbons GH. Vasoactive substances regulate vascular smooth muscle cell apoptosis. Countervailing influences of nitric oxide and angiotensin II. Circ Res 1996;79:748–56.

    Google Scholar 

  53. Yamada T, Horiuchi M, Dzau VJ. Angiotensin II type 2 receptor mediates programmed cell death. Proc Natl Acad Sci USA 1996;93:156–60.

    Google Scholar 

  54. Tanaka M, Ohnishi J, Ozawa Y, et al. Characterization of angiotensin II receptor type 2 during differentiation and apoptosis of rat ovarian cultured granulosa cells. Biochem Biophys Res Comm 1995;207:593–8.

    Google Scholar 

  55. Danser AHJ, Koning MMG, Admiraal PJJ, Derkx FH, Verdouw PD, Schalekamp M. Metabolism of angiotensin I by different tissues in the intact animal. Am J Physiol 1992;263:H418–2.

    Google Scholar 

  56. Admiraal PJJ, Danser AHJ, Jong MS, Pieterman H, Derkx FHM, Schalekamp M. Regional angiotensin II production in essential hypertension and renal artery stenosis. Hypertension 1993;21:173–8.

    Google Scholar 

  57. Campbell DJ. The site of angiotensin production. J Hypert 1985;2:199–207.

    Google Scholar 

  58. Campbell DJ. Circulating and tissue angiotensin systems. J Clin Invest 1986;79:1–6.

    Google Scholar 

  59. Diet F, Pratt RE, Berry GJ, Momose N, Gibbons GH, Dzau VJ. Increased accumulation of tissue ACE in human atherosclerotic coronary artery disease. Circulation 1996;94:2756–67.

    Google Scholar 

  60. Hokimoto S, Yasue H, Fujimoyo K, et al. Expression of angiotensin-converting enzyme in remaining viable myocytes of human ventricles after myocardial infarction. Circulation 1996;84:1513–8.

    Google Scholar 

  61. Paul M, Stock P, Langheinrich M, Liefeldt L, Schonfelder G, Bohm M. Role of the cardiac renin-angiotensin system in human heart failure. Adv Exp Biol 1995;377:279–83.

    Google Scholar 

  62. Passier RC, Smits JF, Verluyten MJ, Studer R, Drexler H, Daemen MJ. Activation of angiotensin-converting enzyme expression in infarct zone following myocardial infarction. Am J Physiol 1995;269:H1268–76.

    Google Scholar 

  63. Danser AHJ, Admiraal PJJ, Derkx FHM, et al. Cardiac renin is kindney-derived. J Hypertens 1993;11(Suppl. 5):S224–5.

    Google Scholar 

  64. Passier RCJJ, Smits JFM, Verluyten MJA, Daemen MJAP. Expression and localization of renin and angiotensinogen in rat heart after myocardial infarction. Am J Physiol 1996;271:H1040–8.

    Google Scholar 

  65. Iwai N, Izumi M, Inagami T, Kinoshita M. Induction of renin in medial smooth muscle cells by balloon injury. Hypertension 1997;29:1044–50.

    Google Scholar 

  66. Passier RCJ, Verluyten MJA, Daemen MJAP, Smits JFM. Regulation of angiotensinogen and renin mRNA expression in different tissues of the rat. In: McGregor GA, Sever PS, eds. Current Advances in ACE-inhibition. v. 3. London: Churchill Livingstone, 1993:150–4.

    Google Scholar 

  67. Doria A, Onuma T, Gearin G, Freire MBS, Warram JH, Krolewski AS. Angiotensinogen polymorphism M235T, hypertension, and nephropathy in insulin-dependent diabetes. Hypertension 1996;27:1134–9.

    Google Scholar 

  68. Castellano M, Muiesan ML, Beschi M, et al. Angiotensin II type 1 receptor A/C-1166 polymorphism. Relationships with blood pressure and cardiovascular structure. Hypertension 1996;28:1076–80.

    Google Scholar 

  69. Lachurié M-L, Azizi M, Guyene T-T, Alhenc-Gelas F, Ménard J. Angiotensin-converting enzyme gene polymorphism has no influence on the circulating renin-angiotensin-aldosterone system or blood pressure in normotensive subjects. Circulation 1995;91:2933–42.

    Google Scholar 

  70. Schmidt S, van Hooft IMS, Grobbee DE, Ganten D, Ritz E. Polymorphism of the angiotensin I converting enzyme gene is apparently not related to high blood pressure: dutch hypertension and offspring study. J Hypertens 1993;11:345–8.

    Google Scholar 

  71. Cambien F, Poirier O, Lecerf L, et al. Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction. Nature 1992;359:641–4.

    Google Scholar 

  72. Ludwig E, Corneli PS, Anderson JL, Marshall HW, Lalouel J-M, Ward RH. Angiotensin-converting enzyme gene polymorphism is associated with myocardial infarction but not with development of coronary stenosis. Circulation 1995;91:2120–4.

    Google Scholar 

  73. Kauma H, Päivänsalo M, Savolainen MJ, et al. Association between angiotensin converting enzyme gene polymorphism and carotid atherosclerosis. J Hypertens 1996;14:1183–7.

    Google Scholar 

  74. McLaughlin KJ, Harden PN, Ueda S, Boulton-Jones JM, Connell JMC, Jardine AG. The role of genetic polymorphisms of angiotensin-converting enzyme in the progression of renal diseases. Hypertension 1996;28:912–5.

    Google Scholar 

  75. Panahloo A, Andrès C, Mohamed-Ali V, et al. The insertion allele of the ACE gene I/D polymorphism. A candidate gene for insulin resistance? Circulation 1995;92:3390–3.

    Google Scholar 

  76. Unger T, Ganten D, Lang RE, Scolkens BA. Is tissue converting enzyme inhibition a determinant of the antihypertensive efficacy of converting enzyme inhibitors? Studies with the two different compounds, Hoe498 and MK421, in spontaneously hypertensive rats. J Cardiovasc Pharmacol 1986;6:872–80.

    Google Scholar 

  77. Strauer BE. Regression of myocardial and coronary hypertrophy in hypertensive heart disease. J Cardiovasc Pharmacol 1988;12(Suppl. 4):45–54.

    Google Scholar 

  78. Dahlöf B, Pennert K, Hansson L. Regression of left ventricular hypertrophy-A meta-analysis. Clin Exp Hypert 1992;A14:173–8.

    Google Scholar 

  79. Ruzicka M, Skarda V, Leenen FHH. Effects of ACE inhibitors on circulating versus cardiac angiotensin II in volume overloadinduced cardiac hypertrophy in rats. Circulation 1995;92:3568–73.

    Google Scholar 

  80. Ruzicka M, Leenen FHH. Relevance of blockade of cardiac and circulatory angiotensin-converting enzyme for the prevention of volume overload-induced cardiac hypertrophy. Circulation 1995;91:16–9.

    Google Scholar 

  81. Powell JS, Muller RKM, Rouge M, Kuhn H, Hefti F, Baumgartner HR. The proliferative response to vascular injury is suppressed by angiotensin-converting enzyme inhibition. J Cardiovasc Pharmacol 1990;16(Suppl. 4):S42–9.

    Google Scholar 

  82. Clozel J-P, Powell JS, Kuhn H, Müller RKM, Hefti F, Baumgartner R. Vascular protection with cilazapril. Drugs 1991;41(Suppl. 1):62–7.

    Google Scholar 

  83. MERCATOR study group. Does the new angiotensin-converting enzyme inhibitor cilazapril prevent restenosis after percutaneous transluminal coronary angioplasty? Circulation 1992;86:100–10.

    Google Scholar 

  84. Lyons D, Webster J, Benjamin N. Effect of enalapril and quinapril on forearm vascular ACE in man. Eur J Clin Pharmacol 1997;51:373–8.

    Google Scholar 

  85. Johnston CI, Jandeleit K, Mooser V, et al. Angiotensin converting enzyme and its inhibition in the heart and blood vessels. J Cardiovasc Pharmacol 1992;20(Suppl. B):S6–S11.

    Google Scholar 

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  1. Departments of Pharmacology and Pathology, Cardiovascular Research Institute Maastricht (CARIM), Universiteit Maastricht, The Netherlands

    Jos F.M. Smits, Robert C.J.J. Passier & Mat J.A.P Daemen

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Smits, J.F., Passier, R.C. & Daemen, M.J. Measurement of patient compliance.. Pharm World Sci 20, 93–99 (1998). https://doi.org/10.1023/A:1008621913932

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