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Angiotensin II Receptor Blockade Physiological and Clinical Implications pp 283–310Cite as

Role of Renin-Angiotensin System in Cardiac Hypertrophy and Failure

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Part of the book series: Progress in Experimental Cardiology ((PREC,volume 2))

Summary

Although the circulatory renin-angiotensin system (RAS) was discovered a century ago, it is only recently that the presence of tissue RAS has become evident. Angiotensin (Ang) II has been demonstrated to influence heart function by effecting cardiac contraction, myocyte growth, cardiac matrix, and cardiac metabolism. These actions are initiated by the binding of Ang II to plasma membrane receptors, namely, AT1 and possibly AT2, which stimulates phospholipase C (PLC) to produce phosphatidylinositol 4,5-bisphosphate, thus forming diacylgjycerol (DAG) and inositol 1,4,5-triphosphate (IP3). An increase in the intracellular Ca2+ appears to result from IP3-mediated release of Ca2+ from the intracellular stores, and this effect may be associated with an increase in cardiac force development. On the other hand, DAG activates protein kinase C (PKC) which stimulates cardiac growth and other actions of Ang II. Intracellular signaling of Ang II-stimulated cardiomyocyte growth may include the activation of tyrosine kinase and mitogen-activated protein kinase (MAPK) cascade. Alterations in different components of RAS, such as renin, angiotensinogen, and angiotensin-converting enzyme (ACE), as well as Ang II receptors (AT1 and AT2), have been shown to occur in different pathological conditions of cardiac hypertrophy and heart failure. On the other hand, ACE genotype has been shown to exhibit a close relationship with myocardial infarction. In this article, we have attempted to review the influence of ACE inhibitors on different types of cardiac hypertrophy and heart failure. Although existing results are controversial, ACE inhibitors, in general, have been shown to exert beneficial effects on cardiac function in myocardial infarction, cardiac hypertrophy from volume or pressure overload, as well as heart failure because of pacing and cardiomyopathy. The possible mechanisms of the effects of ACE inhibitors may include reduction in both circulating and local RAS, scavenging of free radicals, improvement of energy metabolism, modification of the autonomic nervous system, and increase of bradykinin concentration. More importantly, ACE inhibitors may improve cardiac function by remodeling the cell membranes, mobilizing Ca2+, and attenuating the shift in myosin isozymes. Although Ang II receptor antagonists have also been shown to have protective effects on contractile function in cardiac hypertrophy and heart failure, the mechanisms remain to be fully understood.

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References

  1. Tigerstedt R, Bergman PG. 1898. Niere and Kreislauf. Skand Arch Physiol 718:223–271.

    Article  Google Scholar 

  2. Goldblatt H, Lynch J, Hanzal RF, Summerville WW. 1934. Studies on experimental hypertension. 1. The production of persistent elevation of systolic blood pressure by means of renal ischemia. J Exp Med 59:347–379.

    Article  PubMed  CAS  Google Scholar 

  3. Ferguson RK, Brunner HR, Turini GA, Gavras H, McKinstry DN. 1977. A specific orally active inhibitor or angiotensin converting enzyme in man. Lancet 1:775–778.

    Article  PubMed  CAS  Google Scholar 

  4. Gavras H, Brunner HR, Turini GA, Kershaw GR, Tifft GP, Cuttelod S, Gavras I, Vukovich RA, McKinstry DN. 1978. Antihypertensive effect of the oral angiotensin-converting enzyme inhibitor SQ 14225 in man. N Engl J Med 298:991–995.

    Article  PubMed  CAS  Google Scholar 

  5. Heinrikson RL, Poorman RA. 1990. The biochemistry and molecular biology of recombinant human renin and prorenin. In Hypertension: Pathophysiology, diagnosis and management. Ed. JH Laragh and BM Brenner, 1179–1196. New York: Raven Press.

    Google Scholar 

  6. Sigmund CD, Jones CA, Kane CM, Wu C, Lang JA, Gross KW. 1992. Regulated tissue-and cell-specific expression of the human renin gene in transgenic mice. Circ Res 70:1070–1079.

    Article  PubMed  CAS  Google Scholar 

  7. Gomez RA, Chevalier RL, Carey RM, Peach MJ. 1990. Molecular biology of the renal renin angiotensin system. Kidney International 38(Suppl 30):S18–S23.

    Google Scholar 

  8. Clauer E, Gaillard I, Li W, Corvol P. 1989. Regulation of angiotensinogen gene. Am J Hypertens 2:403–410.

    Google Scholar 

  9. Ehlers MRW, Riordan JF. 1990. Angiotensin-converting enzyme: Biochemistry and molecular biology. In: Hypertension: Pathophysiology, diagnosis and management. Ed. JH Laragh and BM Brenner, 1217–1231. New York: Raven Press.

    Google Scholar 

  10. Skidgel RA, Erdos EG. 1987. The broad substrate specificity of human angiotensin I converting enzyme. Clin Exp Hypertens 9A:243–259.

    Article  Google Scholar 

  11. Corvol P, Michaud A, Soubrier F, Williams TA. 1995. Recent advances in knowledge of the structure and function of the angiotensin I converting enzyme. J Hypertens 13(Suppl 3):S3–S10.

    Article  CAS  Google Scholar 

  12. Soubrier F, Alhenc-Gelas F, Hubert C, Allegrine JM, Tregera G, Carvol P. 1988. Two putative active centres in human angiotensin I-converting enzyme revealed by molecular cloning. Proc Natl Acad Sci USA 85:9386–9390.

    Article  PubMed  CAS  Google Scholar 

  13. Bernstein KE, Martin BM, Bernstein EA, Linton J, Striker L, Striker G. 1988. The isolation of angiotensin-converting enzyme cDNA. J Biol Chem 263:11021–11024.

    PubMed  CAS  Google Scholar 

  14. Rigat B, Hubert C, Corvol P, Soubrier F. 1992. PCR detection of the insertion/deletion polymorphism of the human angiotensin converting enzyme gene (DCP1 dipeptidyle carboxy-peptidase 1). Nucleic Acid Res 20:1433.

    Article  PubMed  CAS  Google Scholar 

  15. Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F. 1990. An insertion/ deletion polymorphism in the angiotensin I-converting gene accounting for half the variance of serum enzyme levels. J Clin Invest 86:1343–1346.

    Article  PubMed  CAS  Google Scholar 

  16. Triet L, Kee F, Poirier O, Nicaud V, Lecerf L, Evans A, Cambou J-P, Arveiler D, Luc G, Amouyel P. 1993. Deletion polymorphism in angiotensin-converting enzyme gene associated with parental history of myocardial infarction. Lancet 341:991–993.

    Article  Google Scholar 

  17. Cambien F, Poirier O, Lecerf L, Evans A, Cambou J-P, Arveiler D, Luc G, Bard J-M, Bara L, Ricard S, Tiret L, Amouyel P, Alhenc-Gelas F, Soubrier F. 1992. Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction. Nature 359:641–644.

    Article  PubMed  CAS  Google Scholar 

  18. Samani NJ, Thompson JR, O’Toole L, Charruer K, Woods KL. 1996. A meta-analysis of the association of the deletion altele of the angiotensin-converting enzyme gene with myocardial infarction. Circulation 94:708–712.

    Article  PubMed  CAS  Google Scholar 

  19. Dzau VJ, Sasamura H, Hein L. 1993. Heterogeneity of angiotensin synthetic pathways and receptor subtypes: Physiological and pharmacological implications. J Hypertens 11(Suppl 3):S13–S18.

    CAS  Google Scholar 

  20. Dzau VJ. 1989. Multiple pathways of angiotensin production in the blood vessel wall: Evidence, possibilities and hypotheses. J Hypertens 7:933–936.

    Article  PubMed  CAS  Google Scholar 

  21. Boucher R, Asselin JH, Genest J. 1974. A new enzyme leading to direct formation of Ang II. Circ Res 34(Suppl l):1203–1209.

    Google Scholar 

  22. Liao Y, Husain A. 1995. The chymase-angiotensin system in humans: Biochemistry, molecular biology and potential role in cardiovascular diseases. Can J Cardiol ll(Suppl F):13F–19F.

    Google Scholar 

  23. Urata H, Healy B, Stewart RW, Bumpus FM, Husain A. 1990. Ang II-forming pathways in normal and failing human hearts. Circ Res 66:883–890.

    Article  PubMed  CAS  Google Scholar 

  24. Urata H, Nishimura H, Ganten D. 1995. Mechanisms of Ang II formation in humans. Eur Heart J 16(Suppl N):79–85.

    Article  PubMed  CAS  Google Scholar 

  25. Schunkert H, Ingelfinger JR, Hirsch AT, Pinto Y, Jacob H, Dzau VJ. 1993. Feedback regulation of angiotensin converting enzyme activity and mRNA levels by Ang II. Circ Res 72:312–318.

    Article  PubMed  CAS  Google Scholar 

  26. Biollaz J, Brunner HR, Gavras I, Waeber B, Gavras H. 1982. Antihypertensive relationship to evaluate efficacy of converting enzyme blockade. J Cardiovasc Pharmacol 4:966–972.

    Article  PubMed  CAS  Google Scholar 

  27. Danilov SM, Faerman AI, Printseva TO, Martynov AV, Sakharov IY, Trakht IN. 1987. Immunohistochemical study of angiotensin-converting enzyme in human tissues using monoclonal antibodies. Histochemistry 87:487–490.

    Article  PubMed  CAS  Google Scholar 

  28. Urata H, Boehm KD, Phillip A, Kinoshita A, Gabrovsek J, Bumpus FM, Husain A. 1993. Cellular localization and regional distribution of a major Ang II forming chymase in the heart. J Clin Invest 91:1269–1281.

    Article  PubMed  CAS  Google Scholar 

  29. Chiu AT, Herblin WF, McCall DE, Ardecky RJ, Carini DJ, Duncia JV, Pease LJ, Wong PC, Wexler RR, Johnson AL. 1989. Identification of Ang II receptor subtypes. Biochem Biophys Res Commun 165:196–203.

    Article  PubMed  CAS  Google Scholar 

  30. Whitebread S, Mele M, Kamber B, de Gasparo M. 1989. Preliminary biochemical characterization of two Ang II receptor subtypes. Biochem Biophys Res Commun 163:284–291.

    Article  PubMed  CAS  Google Scholar 

  31. Clauser E, Curnow KM, Davies E, Conchon S, Teutsch B, Vianello B, Monnot C, Corvol P. 1996. Ang II receptors: Protein and gene structures, expression and potential pathological involvement. Eur J Endocrinol 134:403–411.

    Article  PubMed  CAS  Google Scholar 

  32. Szpirer C, Riviere M, Szpirer J, Levan G, Guo DF, Iwai N, Inagami T. 1993. Chromosomal assignment of human and rat hypertension candidate genes: Type 1 Ang II receptor genes and the SA gene. J Hypertens 11:919–925.

    Article  PubMed  CAS  Google Scholar 

  33. Dzau VJ. 1995. Molecular biology of Ang II biosynthesis and receptors. Can J Cardiol ll(Suppl F):21F–26F.

    Google Scholar 

  34. Lin SY, Goodfriend TL. 1970. Angiotensin receptors. Am J Physiol 218:1319–1328.

    PubMed  CAS  Google Scholar 

  35. Regjtz-Zagrosek V, Auch-Schwelk W, Neuss M, Fleck E. 1994. Regulation of the angiotensin receptor subtypes in cell cultures, animal models and human diseases. Eur Heart J 15(Suppl D):92–97.

    Article  Google Scholar 

  36. Della-Bruna R, Ries S, Himmelstoss C, Kurtz A. 1995. Expression of cardiac Ang II AT1 receptor genes in rat hearts is regulated by steroids but not by Ang II. J Hypertens 13:763–769.

    PubMed  CAS  Google Scholar 

  37. Dzau VJ, Mukoyama M, Pratt RE. 1994. Molecular biology of angiotensin receptors: Target for drug research? J Hypertens 12(Suppl 2):S1–S5.

    CAS  Google Scholar 

  38. Murphy TJ, Alexander RW, Griendling KK, Runge MS, Bernstein KE. 1991. Isolation of a cDNA encoding the vascular type-1 angiotensin receptor. Nature 351:233–236.

    Article  PubMed  CAS  Google Scholar 

  39. van Heugten HAA, Eskildsen YEG, de Jonge HW, Bezstarosti K, Lamers JMJ. 1996. Phosphoinositide-generated messengers in cardiac signal transduction. Mol Cell Biochem 157:5–14.

    Article  PubMed  Google Scholar 

  40. Duff JL, Marrero MB, Paxton WG, Schieffer B, Bernstein KE, Berk BC. 1995. Ang II signal transduction and the mitogen-activated protein kinase pathway. Cardiovasc Res 30:511–517.

    PubMed  CAS  Google Scholar 

  41. Inagami K, Yamano Y, Bardhan S, Chaki S, Guo DF, Ohyama K, Kambayashi Y. 1995. Cloning, expression and regulation of Ang II receptors. Adv Exp Med Biol 377:311–317.

    PubMed  CAS  Google Scholar 

  42. Sadoshima JI, Izumo S. 1993. Signal transduction pathways of angiotensin II induced c-fos gene expression in cardiac myocytes in vitro. Roles of phospholipase-derived second messengers. Circ Res 73:424–438.

    Article  PubMed  CAS  Google Scholar 

  43. Marrero MB, Schieffer B, Paxton WG, Duff JL, Berk BC, Bernstein KE. 1995. The role of tyrosine phosphorylation in Ang II-mediated intracellular signalling. Cardiovasc Res 30:530–536.

    PubMed  CAS  Google Scholar 

  44. Yamada T, Horiuchi M, Dzau VJ. 1996. Ang II type 2 receptor mediates programmed cell death. Proc Natl Acad Sci USA 93:156–160.

    Article  PubMed  CAS  Google Scholar 

  45. Kijima K, Matsubara H, Murasawa S, Maruyama K, Ohkubo N, Mori Y, Inada M. 1995. Regulation of angiotensin type 2 receptor gene by the protein kinase C-calcium pathway. Hypertension 216:359–366.

    CAS  Google Scholar 

  46. Jin M, Wilhelm MJ, Lang RE, Unger T, Lindpaintner K, Ganten D. 1988. Endogenous tissue renin-angiotensin system. Am J Med 84(Suppl 3A):28–36.

    Article  PubMed  CAS  Google Scholar 

  47. Johnston CI. 1992. Renin-angiotensin system: A dual tissue and hormonal system for cardiovascular control. J Hypertens 10(Suppl 7):S13–S26.

    CAS  Google Scholar 

  48. Danser AHJ. 1996. Local renin-angiotensin system. Mol Cell Biochem 157:211–216.

    Article  PubMed  CAS  Google Scholar 

  49. Lindpaintner K, Ganten D. 1991. The cardiac renin-angiotensin system: An appraisal of present experimental and clinical evidence. Circ Res 68:905–921.

    Article  PubMed  CAS  Google Scholar 

  50. Dzau VJ. 1988. Cardiac renin-angiotensin system: Molecular and functional aspects. Am J Med 84(Suppl 3A):22–27.

    Article  PubMed  CAS  Google Scholar 

  51. Paul M, Bachmann J, Ganten D. 1992. The tissue renin-angiotensin system in cardiovascular disease. Trends Cardiovasc Med 2:94–99.

    Article  PubMed  CAS  Google Scholar 

  52. Campbell DJ. 1987. Circulating and tissue renin-angiotensin systems. J Clin Invest 79:1–6.

    Article  PubMed  CAS  Google Scholar 

  53. Dzau VJ, Re RN. 1987. Evidence for the renin in the heart. Circulation 73(Suppl 2):S33–S38.

    Google Scholar 

  54. Nakayama K, Tanata T, Nakanishi S. 1986. Tissue distribution of rat angiotensinogen mRNA and structure analysis of its heterogeneity. J Biol Chem 261:319–323.

    PubMed  Google Scholar 

  55. Campbell DJ, Habener JF. 1986. The angiotensinogen gene is expressed and differentially regulated in multiple tissues of the rat. J Clin Invest 78:31–39.

    Article  PubMed  CAS  Google Scholar 

  56. Kunapuli SP, Kumar A. 1987. Molecular cloning of human angiotensinogen cDNA and evidence for the presence of its mRNA in the rat heart. Circ Res 60:786–790.

    Article  PubMed  CAS  Google Scholar 

  57. Sawa H, Tokuchi F, Mochizuki N, Mochizuki N, Endo Y, Furuta Y, Shinohara T, Takada A, Kawaguchi H, Yasuda H, Nagashima K. 1992. Expression of the angiotensinogen gene and localization of its protein in the human heart. Circulation 86:138–146.

    Article  PubMed  CAS  Google Scholar 

  58. von Lutterotti N, Catanzaro DF, Sealeay JE, Laragh JH. 1994. Renin is not synthesized by cardiac and extrarenal vascular tissues. A review of experimental evidence. Circulation 89:458–470.

    Article  Google Scholar 

  59. Lindpaintner K, Jin M, Niedermajer N, Wilhelm MJ, Ganten D. 1990. Cardiac angiotensinogen and its local activation in the isolated perfused beating heart. Circ Res 67:564–573.

    Article  PubMed  CAS  Google Scholar 

  60. Yamada H, Fabris B, Allen AM, Jackson B, Johnston CI, Mendelsohn FAO. 1991. Localization of angiotensin converting enzyme in rat heart. Circ Res 68:141–149.

    Article  PubMed  CAS  Google Scholar 

  61. Sun Y, Ratajska A, Zhou G, Weber KT. 1993. Angiotensin converting enzyme and myocardial fibrosis in the AT receiving Ang II or aldosterone. J Lab Clin Med 122:395–403.

    PubMed  CAS  Google Scholar 

  62. Sun Y, Cleutjens JPM, Diaz-Arias AA, Weber KT. 1994. Cardiac angiotensin converting enzyme and myocardial fibrosis in the rat. Cardiovasc Res 28:1423–1432.

    Article  PubMed  CAS  Google Scholar 

  63. Hoit BD, Shao Y, Kinoshita A, Gabel M, Husain A, Walsh RA. 1995. Effects of Ang II generated by an angiotensin-converting enzyme independent pathway on left ventricular performance in the conscious baboon. J Clin Invest 95:1519–1527.

    Article  PubMed  CAS  Google Scholar 

  64. Baker KM, Campanile CP, Trachte GJ, Peach MJ. 1984. Identification of the rabbit Ang II myocardial receptor. Circ Res 54:286–293.

    Article  PubMed  CAS  Google Scholar 

  65. Lokuta AJ, Cooper C, Caa ST, Wang HE, Rogers TB. 1994. Ang II stimulates the release of phospholipid-derived second messengers through multiple receptor subtypes in heart cells. J Biol Chem 269:4832–4838.

    PubMed  CAS  Google Scholar 

  66. Koch-Weser J. 1965. Nature of the inotropic action of angiotensin on the ventricular myocardium. Circ Res 16:239-237.

    Google Scholar 

  67. Ishihata A, Endoh M. 1995. Species-related differences in inotropic effects of Ang II in mammalian ventricular muscle: Receptors, subtype and phosphoinositide hydrolysis. Br J Pharmacol 114:447–453.

    Article  PubMed  CAS  Google Scholar 

  68. Yamazaki T, Komuro I, Shiojimo I, Yazaki Y. 1996. The renin-angiotensin system and cardiac hypertrophy. Heart 76(Suppl 3):33–35.

    Article  PubMed  CAS  Google Scholar 

  69. Allen I, Cohen NM, Dhallan RS, Gaa ST, Lederer WJ, Rogers TB. 1988. Ang II increases spontaneous contractile frequency and stimulates calcium current in cultures neonatal rat heart myocytes: Insight into underlying biochemical mechanisms. Circ Res 62:524–534.

    Article  PubMed  CAS  Google Scholar 

  70. Freer R, Pappano A, Peach M, Ning K, McLean M, Vogel S, Sperelakis N. 1976. Mechanism for the positive inotropic effect of Ang II on isolated cardiac muscle. Circ Res 39:178–183.

    Article  PubMed  CAS  Google Scholar 

  71. Bonnardeaux JL, Regoli D. 1974. Action of angiotensin and analogues on the heart. Can J Physiol Pharmacol 52:50–60.

    Article  PubMed  CAS  Google Scholar 

  72. Cross RB, Chalk J, South M, Liss B. 1981. The action of angiotensin on the isolated cat heart. Life Sci 29:903–908.

    Article  PubMed  CAS  Google Scholar 

  73. Zhang J, Pfaffendorf M, van Zwieten PA. 1995. Hemodynamic effects of Ang II and the influence of angiotensin receptor antagonists in pithed rabbits. J Cardiovasc Pharmacol 25:724–731.

    Article  PubMed  CAS  Google Scholar 

  74. Ikenouchi H, Barry WH, Bridge JHB, Weinberg EO, Apstein CS, Lorell BH. 1994. Effects of Ang II on intracellular Ca2+ and pH in isolated beating rabbit hearts and myocytes loaded with the indicator indo-1. J Physiol 48:203–215.

    Google Scholar 

  75. Huang H, Li P, Hamby CV, Reiss K, Meggs LG, Anversa P. 1994. Alteration in Ang II receptor mediated signal transduction shortly after coronary artery constriction in the rat. Cardiovasc Res 28:1564–1573.

    Article  PubMed  CAS  Google Scholar 

  76. Lkeda U, Maeda Y, Kawahara Y, Yokoyama M, Shimada K. 1995. Ang II augments cytosine-stimulated nitric oxide synthesis in rat cardiac myocytes. Circulation 92:2683–2689.

    Article  Google Scholar 

  77. Zhu YC, Zhu YZ, Spitznagel H, Gohlke P, Unger T. 1996. Substrate metabolism, hormone interaction, and angiotensin-converting enzyme inhibitors in left ventricular hypertrophy. Diabetes 45(Suppl 1):S59–S65.

    PubMed  Google Scholar 

  78. Schlueter W, Keilani T, Batlle DC. 1993. Metabolic effects of converting enzyme inhibitors: Focus on the reduction of cholesterol and lipoprotein (a) by fosinopril. Am J Cardiol 72:37H–44H.

    Article  PubMed  CAS  Google Scholar 

  79. Zimmermann B. 1981. Adrenergic facilitation by angiotensin: Does it serve a physiologic function? Clin Sci 60:343–348.

    Google Scholar 

  80. Xiang J, Linz W, Becker H, Ganten D, Lang RE, Scholkens B, Unger T. 1985. Effects of converting enzyme inhibitors ramipril and enalapril on peptide action and sympathetic neurotransmission in the isolated heart. Eur J Pharmacol 113:215–223.

    Article  PubMed  CAS  Google Scholar 

  81. Eckberg DL, Drabinsky M, Braunwald E. 1971. Defective cardiac parasympathetic control in patients with heart disease. N Engl J Med 285:877–883.

    Article  PubMed  CAS  Google Scholar 

  82. Osterziel KJ, Hänlein D, Dietz R. 1994. Interactions between the renin-angiotensin system and the parasympathetic nervous system in heart failure. J Cardiovasc Pharmacol 24(Suppl 2):S70–S74.

    PubMed  CAS  Google Scholar 

  83. Guo GB, Abboud FM. 1984. Ang II attenuates baroreflex control of heart rate and sympathetic activity. Am J Physiol 264:H80–H89.

    Google Scholar 

  84. Arnaudeau S, Macrez-Lepretre N, Mironneau J. 1996. Activation of calcium sparks by Ang II in vesicular myocytes. Biochem Biophys Res Commun 24:809–815.

    Article  Google Scholar 

  85. Macrez LN, Morel JL, Mironneau J. 1996. Ang II-mediated activation of L-type calcium channels involved phosphatidylinositol hydrolysis-independent activation of protein kinase C in rat portal vein myocytes. J Pharmacol Exp Ther 278:468–475.

    Google Scholar 

  86. Baker KM, Singer HA, Aceto JF. 1989. Ang II receptor-mediated stimulation of cytosolic-free calcium and inositol phosphates in chick myocytes. J Pharmacol Exp Ther 251:578–585.

    PubMed  CAS  Google Scholar 

  87. Barry WH, Matsui H, Bridge JH, Spitzer KW. 1995. Excitation-contraction coupling in ventricular myocytes: Effects of Ang II. Adv Exp Med Biol 382:31–39.

    Article  PubMed  CAS  Google Scholar 

  88. Dösemeci A, Dhallan RS, Cohen NM, Lederer WJ, Rogers TB. 1988. Phorbol ester increases calcium current and stimulates the effects of Ang II on cultures neonatal rat heart myocytes. Circ Res 62:347–357.

    Article  PubMed  Google Scholar 

  89. Aceto JF, Baker KM, 1990. [Sar1] Ang II receptor-mediated stimulation of protein synthesis in chick heart cells. Am J Physiol 258.H806–H813.

    PubMed  CAS  Google Scholar 

  90. Baker KM, Aceto JF. 1990. Ang II stimulation of protein synthesis and cell growth in chick heart cells. Am J Physiol 259:H610–H618.

    PubMed  CAS  Google Scholar 

  91. Greenen DL, Malhotra A, Scheuer J. 1993. Ang II increases cardiac protein synthesis in adult rat heart. Am J Physiol 265:H238–H243.

    Google Scholar 

  92. van Krimpen C, Smits JFM, Cleutjens JPM, Debets JJM, Schoemaker RG, Struyker Boudier HAJ, Bosman FT, Daemen MJAP. 1991. DNA synthesis in the non-infarcted cardiac interstitium after left coronary artery ligation in the rat: Effects of captopril. J Mol Cell Cardiol 23:1245–1253.

    Article  PubMed  Google Scholar 

  93. Fisher SA, Absher M. 1995. Norepinephrine and ANG II stimulate secretion of TGF-ß by neonatal rat cardiac fibroblasts in vitro. Am J Physiol 268:C910–C917.

    PubMed  CAS  Google Scholar 

  94. Kato H, Suzuki H, Tajima S, Ogata Y, Tominaga T, Sato A, Saruta T. 1991. Ang II stimulates collagen synthesis in cultured vascular smooth muscle cells. J Hypertens 9:17–22.

    PubMed  CAS  Google Scholar 

  95. Schorb W, Booz GW, Dostal DE, Conrad KM, Chang KC, Baker KM. 1993. Ang II is mitogenic in neonatal rat cardiac fibroblasts. Circ Res 72:1245–1254.

    Article  PubMed  CAS  Google Scholar 

  96. Morgan HE, Baker KM. 1991. Cardiac hypertrophy: Mechanical, neural and endocrine dependencies. Circulation 83:13–26.

    Article  PubMed  CAS  Google Scholar 

  97. Dhalla NS, Das PK, Sharma GP. 1978. Subcellular basis of cardiac contractile failure. J Mol Cell Cardiol 10:363–385.

    Article  PubMed  CAS  Google Scholar 

  98. Dhalla NS, Pierce GN, Panagia V, Singal PK, Beamish RE. 1982. Calcium movements in relation to heart function. Basic Res Cardiol 77:117–139.

    Article  PubMed  CAS  Google Scholar 

  99. Schunkert H, Jackson B, Tang SS, Schoen FJ, Smits JFM, Apstein CS, Lorell BH. 1993. Distribution and functional significance of cardiac angiotensin converting enzyme in hypertrophied rat hearts. Circulation 87:1328–1339.

    Article  PubMed  CAS  Google Scholar 

  100. Harrap SB, Dominiczak AF, Fraser R, Lever AF, Morton JJ, Foy CJ, Watt GCM. 1996. Plasma Ang II, predisposition to hypertension and left ventricular size in healthy young adults. Circulation 93:1148–1154.

    Article  PubMed  CAS  Google Scholar 

  101. Ohta K, Kim S, Wanibuchi H, Ganten D, Iwao H. 1996. Contribution of local renin-angiotensin system to cardiac hypertrophy, phenotypic modulation, and remodeling in TGR(mREN2)27 transgenic rats. Circulation 94:785–791.

    Article  PubMed  CAS  Google Scholar 

  102. Bader M, Zhao Y, Sander M, Lee MA, Bachmann J, Böhm M, Djavidani B, Peters J, Mullins JJ, Ganten D. 1992. Role of tissue renin in the pathophysiology of hypertension in TGR(mREN2)27 rats. Hypertension 19:681–686.

    Article  PubMed  CAS  Google Scholar 

  103. Böhm M, Lee MA, Krauts R, Kim S, Schinke M, Djavidani B, Wagner J, Kaling M, Wirnen W, Bader M, Ganten D. 1995. Ang II receptor blockade in TGR(mREN2)27: Effect of renin-angiotensin-system gene expression and cardiovascular functions. J Hypertens 13:891–899.

    Article  PubMed  Google Scholar 

  104. Kawaguchi H, Kitabatake A. 1995. Renin-angiotensin system in failing heart. J Mol Cell Cardiol 27:201–209.

    Article  PubMed  CAS  Google Scholar 

  105. Weber KT, Sun Y, Tyagi SC, Cleutjens JPA. 1994. Collagen network of the myocardium: Function, structure remodeling and regulatory mechanisms. J Mol Cell Cardiol 26:279–292.

    Article  PubMed  CAS  Google Scholar 

  106. Boluyt MO, O’Neill L, Meredith AL, Bing OHL, Brooks WW, Conrad CH, Crow MT, Lakatta EG. 1994. Alterations in cardiac gene expression during the transition from stable hypertrophy to heart failure: Marked upregulation of gene encoding extracellular matrix components. Circ Res 75:23–32.

    Article  PubMed  CAS  Google Scholar 

  107. Kim S, Ohta K, Hamaguchi A, Omura T, Yukimura T, Miura K, Inada Y, Ishimura Y, Chatani F, Iwao H. 1995. Ang II type 1 receptor antagonists inhibit the gene expression of transforming growth factor-β1 and extracellular matrix in cardiac and vascular tissues of hypertensive rats. J Pharmacol Exp Ther 273:509–515.

    PubMed  CAS  Google Scholar 

  108. Iwani K, Ashizawa N, Do YS, Graf K, Hsueh W. 1996. Comparison of ANG II with other growth factors on EGR-I and matrix gene expression in cardiac fibroblast. Am J Physiol 270:H2100–H2107.

    Google Scholar 

  109. Hsueh WA, Do YS, Anderson PW, Law RE. 1995. Ang II in cell growth and matrix production. Adv Exp Med Biol 377:217–223.

    PubMed  CAS  Google Scholar 

  110. Brilla CG, Zhou G, Rupp H, Maisch B, Weber KT. 1995. Role of Ang II and prostaglandin E2 in regulating cardiac fibroblast collagen turnover. Am J Cardiol 76:8D–13D.

    Article  PubMed  CAS  Google Scholar 

  111. Crawford D, Chobanian AV, Brecher P. 1994. Ang II induced fibronectin expression associated with cardiac fibrosis in the rat. Circ Res 74:727–739.

    Article  PubMed  CAS  Google Scholar 

  112. Dostal DE, Booz GW, Baker KM. 1996. Ang II signaling pathways in cardiac fibroblasts: Conventional versus novel mechanisms in mediating cardiac growth and function. Mol Cell Biochem 157:15–21.

    Article  PubMed  CAS  Google Scholar 

  113. Sadoshima JI, Xu Y, Slayter HS, Izumo S. 1993. Autocrine release of Ang II mediated stretch-induced hypertrophy of cardiac myocytes in vitro. Cell 75:977–984.

    Article  PubMed  CAS  Google Scholar 

  114. Kent RL, McDermott PJ. 1996. Passive load and Ang II evoke differential responses of gene expression and protein synthesis in cardiac myocytes. Circ Res 78:829–838.

    Article  PubMed  CAS  Google Scholar 

  115. Reiss K, Capasso JM, Huang HE, Meggs LG, Li P, Anversa P. 1993. Ang II receptors, c-myc, and c-jun in myocytes after myocardial infarction and ventricular failure. Am J Physiol 264:H760–H769.

    PubMed  CAS  Google Scholar 

  116. Lee AA, Dillmann WH, McCulloch AD, Villarreal FJ. 1995. Ang II stimulates the autocrine production of transforming growth factor-β1 in adult rat cardiac fibroblasts. J Mol Cell Cardiol 27:2347–2357.

    Article  PubMed  CAS  Google Scholar 

  117. Du J, Meng XP, Delafontaine P. 1996. Transcriptional regulation of the insulin-like growth factor-I receptor gene: Evidence for protein kinase C-dependent and independent pathways. Endocrinology 137:1378–1384.

    Article  PubMed  CAS  Google Scholar 

  118. Everett AD, Tufro-McReddie A, Fisher A, Gomez RA. 1994. Angiotensin receptor regulates cardiac hypertrophy and transforming growth factor-β1 expression. Hypertension 23:587–592.

    Article  PubMed  CAS  Google Scholar 

  119. Booz GW, Taher MM, Baker KM, Singer HA. 1994. Ang II induces phosphatidic acid formation in neonatal rat fibroblasts: Evaluation of the roles of phospholipases C and D. Mol Cell Biochem 141:135–143.

    Article  PubMed  CAS  Google Scholar 

  120. Booz GW, Dostal DE, Singer HA, Baker KM. 1994. Involvement of protein kinase C and Ca2+ in Ang II-induced mitogenesis of cardiac fibroblasts. Am J Physiol 267:C1308–C1318.

    PubMed  CAS  Google Scholar 

  121. Bogoyevitch MA, Glennon PE, Andersson MB, Clerk A, Lazou A, Marshall CJ, Parker PJ, Sugden PH. 1994. Endothelin-I and fibroblast growth factors stimulate the mitogen-activated protein kinase signaling cascade in cardiac myocytes. The potential role of the cascade in the integration of two signaling pathways leading to myocyte hypertrophy. J Biol Chem 269:1110–1119.

    PubMed  CAS  Google Scholar 

  122. Ishiye M, Umemura K, Uematsu T, Nakashima M. 1995. Effects of losartan, an Ang II antagonist, on the development of cardiac hypertrophy to volume overload. Biol Pharm Bull 18:700–704.

    Article  PubMed  CAS  Google Scholar 

  123. Federico Pieruzzi F, Xaid A, Abassi ZA, Keiser HR. 1995. Expression of renin-angiotensin system components in the heart, kidneys, and lungs of rats with experimental heart failure. Circulation 92:3105–3112.

    Article  Google Scholar 

  124. Schunkert H, Dzau VJ, Tong SS, Hirsch AT, Apstein CS, Lorell BH. 1990. Increased rat cardiac angiotensin converting enzyme activity and mRNA levels in pressure overload left ventricular hypertrophy: Effects on coronary resistance, contractility and relaxation. J Clin Invest 86:1913–1920.

    Article  PubMed  CAS  Google Scholar 

  125. Iwai N, Shimoike H, Kinoshita M. 1995. Cardiac renin-angiotensin system in the hypertrophied heart. Circulation 92:2690–2696.

    Article  PubMed  CAS  Google Scholar 

  126. Sun Y, Weber KT. 1996. Cells expressing Ang II receptors in fibrous tissues of rat heart. Cardiovasc Res 31:518–525.

    PubMed  CAS  Google Scholar 

  127. Zhang X, Dostal DE, Reiss K, Cheng W, Kajstura J, Li P, Huang H, Sonnenblick EH, Meggs L, Baker KM, Anversa P. 1995. Identification and activation of automne renin-angiotensin system in adult ventricular myocytes. Am J Physiol 269:H1791–H1802.

    PubMed  CAS  Google Scholar 

  128. Hirsh AT, Talsness CE, Schunlert H, Paul M, Dzau VJ. 1991. Tissue-specific activation of cardiac angiotensin converting enzyme in experimental heart failure. Circ Res 69:475–482.

    Article  Google Scholar 

  129. Nio Y, Matsubara H, Murasawa S, Kanasaki M, Inada M. 1995. Regulation of gene transcription of Ang II receptor subtypes in myocardial infarction. J Clin Invest 95:46–54.

    Article  PubMed  CAS  Google Scholar 

  130. Tang SS, Diamant D, Rogg H, Schunkert H, Lorell BH, Ingelfinger JR. 1992. Rat hearts contain Ang II (ANGII) receptors that are downregulated and differentially expressed during hypertrophy (abstract). Hypertension 20:418.

    Google Scholar 

  131. Nishimura J, Kobayashi S, Chen X, Shikasho T, Kanaide H. 1992. Ang II receptor mRNA is regulated by Ang II: Possible involvement of protein kinase C in receptor downregulation (abstract). Circulation 86(Suppll):I–289.

    Article  Google Scholar 

  132. Suzuki J, Matsubara H, Urakami M, Inada M. 1993. Rat Ang II (type 1) receptor mRNA regulation and subtype expression in myocardial growth and hypertrophy. Circ Res 73:439–447.

    Article  PubMed  CAS  Google Scholar 

  133. Meggs LG, Coupet J, Huang H, Cheng W, Li P, Capes JM, Homcy CJ, Anversa P. 1993. Regulation of Ang II receptors on ventricular myocytes after myocardial infarction in rats. Circ Res 72:1149–1162.

    Article  PubMed  CAS  Google Scholar 

  134. Zagrosek VR, Friedel N, Heymann A, Bauer P, Rolfs A, Steffen C, Hildebrandt A, Whether R, Fleck E. 1995. Regulation, chamber localization, and subtype distribution of Ang II receptors in human hearts. Circulation 91:1461–1471.

    Article  Google Scholar 

  135. Schunker H, Tang SS, Litwin SE, Diamant D, Riegger G, Dzau VJ, Ingelfinger JR. 1993. Regulation of intrarenal and circulating renin-angiotensin systems in severe heart failure in the rat. Cardiovasc Res 27:731–735.

    Article  Google Scholar 

  136. Raynolds MV, Bristow MR, Bush EW, Abraham WT, Lowes BD, Zisman LS, Taft CS, Perryman MB. 1993. Angiotensin-converting enzyme DD genotype in patients with ischemic or idiopathic dilated cardiomyopathy. Lancet 342:1073–1075.

    Article  PubMed  CAS  Google Scholar 

  137. Pinto YM, van Gilst WH, Kingma JH, Schunkert H. 1995. Captopril and thrombolysis study investigators. Deletion type altele of the angiotensin-converting enzyme gene is associated with progressive ventricular dilation after anterior myocardial infarction. J Am Coll Cardiol 25:1622–1626.

    Article  PubMed  CAS  Google Scholar 

  138. Arbustini E, Grasso M, Fasani R, Klersy C, Diegoli M, Porcu E, Banchieri N, Fortina P, Danesino C, Specchia G. 1995. Angiotensin converting enzyme gene deletion altele is independently and strongly associated with coronary atherosclerosis and myocardial infarction. Br Heart J 74:584–591.

    Article  PubMed  CAS  Google Scholar 

  139. Gharavi AG, Lipkowitz MS, Diamond JA, Jhang JS, Phillips RA. 1996. Deletion polymorphism of the angiotensin-converting enzyme gene is independently associated with left ventricular mass and geometric remodeling in systemic hypertension. Am J Cardiol 77:1315–1319.

    Article  PubMed  CAS  Google Scholar 

  140. Andersson B, Sylvén C. 1996. The DD genotype of the angiotensin-converting enzyme gene is associated with increased mortality in idiopathic heart failure. J Am Coll Cardiol 28:162–167.

    Article  PubMed  CAS  Google Scholar 

  141. Schunkert H, Hense HW, Holmer SR, Stender M, Perz S, Kell U, Lorell BH, Riegger GAJ. 1994. Association between a deletion polymorphism of the angiotensin-converting-enzyme gene and left ventricular hypertrophy. N Engl J Med 330:1634–1638.

    Article  PubMed  CAS  Google Scholar 

  142. Lindpaintner K, Lee M, Larson MG, Rao VS, Pfeffer MA, Ordovas O, Schaefer EJ, Wilson AF, Wilson PWF, Vasan RS, Myers RH, Levy D. 1996. Absence of association or genetic between the angiotensin-converting-enzyme gene. N Engl J Med 334:1023–1028.

    Article  PubMed  CAS  Google Scholar 

  143. Ondertti MA, Rubin B, Cushman DW. 1997. Design of specific inhibitors of angiotensin converting enzyme: New class of orally active antihypertensive agents. Science 196:441–443.

    Article  Google Scholar 

  144. Juggi JS, Berard GK, van Gilst WH. 1993. Cardioprotection by angiotensin-converting enzyme (ACE) inhibitors. Can J Cardiology 9:336–352.

    CAS  Google Scholar 

  145. Cohen ML. 1985. Synthetic and fermentation-derived angiotensin-converting enzyme inhibitors. Ann Rev Pharmacol Toxicol 25:307–323.

    Article  CAS  Google Scholar 

  146. Braunwald E. 1991. ACE inhibitors—a cornerstone of the treatment of heart failure. N Engl J Med 325:351–353.

    Article  PubMed  CAS  Google Scholar 

  147. Opie LH. 1995. Fundamental role of angiotensin-converting enzyme inhibitors in the management of congestive heart failure. Am J Cardiol 75:3F–6F.

    Article  PubMed  CAS  Google Scholar 

  148. Pfeffer MA, Braunwald E. 1990. Ventricular remodeling after myocardial infarction. Experimental observation and clinical implications. Circulation 81:1161–1172.

    Article  PubMed  CAS  Google Scholar 

  149. Raya TE, Gay RG, Aguirre M, Goldman S. 1989. Importance of vasodilatation in prevention of left ventricular dilatation after chronic large myocardial infarction in rats: A comparison of captopril and hydrazine. Circ Res 64:330–337.

    Article  PubMed  CAS  Google Scholar 

  150. Mehta PM, Alker KJ, Kloner RA. 1988. Functional infarct expansion, left ventricular dilatation, and isovolume in occlusion: A two dimensional echocardiographic study. J Am Coll Cardiol 11:630–636.

    Article  PubMed  CAS  Google Scholar 

  151. Sweet CS. 1990. Issues surrounding a local cardiac renin system and the beneficial actions of angiotensin-converting enzyme inhibitors in ischemic myocardium. Am J Cardiol 65:111–113.

    Article  Google Scholar 

  152. Litwin SE, Litwin CM, Raya TE, Warner AL, Goldman S. 1991. Contractility and stiffness of noninfarcted myocardium after coronary ligation in rats. Effects of chronic angiotensin converting enzyme inhibition. Circulation 83:1028–1037.

    Article  PubMed  CAS  Google Scholar 

  153. Pfeffer JM, Pfeffer MA, Braunwald E. 1985. Influence of chronic captopril therapy on the infarcted left ventricle of the rat. Circ Res 57:84–95.

    Article  PubMed  CAS  Google Scholar 

  154. Lefer AM, Peck RC. 1984. Cardioprotective effects of enalapril in acute myocardial ischemia. Pharmacology 29:61–69.

    Article  PubMed  CAS  Google Scholar 

  155. Ertl G, Kloner RA, Alexander W, Braunwald E. 1982. Limitation of experimental infarct size by an angiotensin-converting enzyme inhibitor. Circulation 65:40–48.

    Article  PubMed  CAS  Google Scholar 

  156. Daniell HB, Carson RR, Ballard KD, Tomas GR, Privitera PJ. 1984. Effect of captopril on limiting infarct size in conscious dogs. J Cardiovasc Pharmacol 6:1043–1047.

    PubMed  CAS  Google Scholar 

  157. Liang CS, Gavras H, Black J, Sherman LG, Hood WB. 1982. Renin-angiotensin system in acute myocardial infarction in dogs. Effects on systemic hemodynamics, myocardial blood flow, segmental myocardial function and infarct size. Circulation 66:1249–1255.

    Article  PubMed  CAS  Google Scholar 

  158. Leddy CL, Wilen M, Francious JA. 1983. Effects of a new angiotensin converting enzyme inhibitor, enalapril, in acute and chronic left ventricular failure. J Clin Pharmacol 23:189–198.

    Article  PubMed  CAS  Google Scholar 

  159. Hock CE, Riberiro LGT, Lefer AM. 1985. Prevention of ischemic myocardium by a new converting enzyme inhibitor, enalapril acid. Am Heart J 109:222–228.

    Article  PubMed  CAS  Google Scholar 

  160. Jeremic G, Masson S, Luvarà G, Porzio S, Lagrasta C, Riva E, Olivetti G, Latini R. 1996. Effects of new angiotensin-converting enzyme inhibitor (idrapril) in rats with left ventricular dysfunction after myocardial infarction. J Cardiovasc Pharmacol 27:347–354.

    Article  PubMed  CAS  Google Scholar 

  161. Pfeffer MA, Braunwald E, Moyé LA, Basta L, Brown EJ, Cuddy TE, Davis BR, Geltman EM, Goldman S, Flaker GC. 1992. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 327:669–677.

    Article  PubMed  CAS  Google Scholar 

  162. Emmert SE, Stabilito II, Sweet CS. 1987. Acute and subacute hemodynamic effects of enalaprilat, milrinone and combination therapy in rats with chronic left ventricular dysfunction. Clin Exp Ther Prac A9:297–306.

    CAS  Google Scholar 

  163. Fornes P, Richer C, Pussard E, Heudes D, Domergue V, Giudicelli JF. 1992. Beneficial effects of trandolapril on experimental induced congestive heart failure in rats. Am J Cardiol 70:43D–51D.

    Article  PubMed  CAS  Google Scholar 

  164. Beermann A, Nyquist O, Höglund C, Jacobsson KA, Näslund U, Jensen-Urstad M. 1993. Acute haemodynamic effects and pharmacokinetics of ramipril in patients with heart failure. A placebo controlled three-dose study. Eur J Clin Pharmacol 45:241–246.

    Article  PubMed  CAS  Google Scholar 

  165. Pfeffer MA, Lamas GA, Vaughan DE, Parisi AF, Braunwald E. 1988. Effect of captopril on progressive ventricular dilatation after anterior myocardial infarction. N Engl J Med 319:80–86.

    Article  PubMed  CAS  Google Scholar 

  166. Anning PB, Grocott RM, Lewis MJ, Shah AM. 1995. Enhancement of left ventricular relaxation in the isolated heart by an angiotensin converting enzyme inhibitor. Circulation 92:2660–2665.

    Article  PubMed  CAS  Google Scholar 

  167. The SOLVD Investigators. 1992. Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection. N Engl J Med 327:685–691.

    Article  Google Scholar 

  168. Ambrosio E, Borghi C, Magnani B. 1995. For the survival of myocardial infarction long-term evaluation (SMILE) study investigation. The effect of the angiotensin-converting-enzyme inhibitor zofenopril on mortality and morbidity after anterior myocardial infarction. N Engl J Med 332:80–85.

    Article  Google Scholar 

  169. ISIS-4 (Fourth international study of infarct survival) collaborative group. 1995. ISIS-4: A randomized factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58050 patients with suspected acute myocardial infarction. Lancet 345:669–685.

    Article  Google Scholar 

  170. Swedberg K, Held P, Kjekshus J and CONSENSUS II Investigators. 1992. Effects of the early administration of enalapril on mortality in patients with acute myocardial infarction. Results of the Cooperative New Scandinavian Enalapril Survival Study II (CONSENSUS-II). N Engl J Med 327:678–684.

    Article  PubMed  CAS  Google Scholar 

  171. Gruppo italiano per lo studio delia sopravvivenza nell’infarto miocardico. 1996. Six-month effects of early treatment with lisinopril and transdermal glyceryl trinitrate singly and together withdrawn six weeks after acute myocardial infarction: The GISSI-3 trial. J Am Coll Cardiol 27:337–344.

    Google Scholar 

  172. Cleland JG, Puri S. 1994. How do ACE inhibitor reduce mortality in patients with left ventricular dysfunction with or without heart failure: Remodeling, resetting, or sudden death? Br Heart J 72(Suppl 3):S81–S86.

    Article  PubMed  CAS  Google Scholar 

  173. Beckwith C, Munger MA. 1993. Effect of angiotensin-converting enzyme inhibitor on ventricular remodeling and survival following myocardial infarction. Ann Pharmacotherap 27:755–766.

    CAS  Google Scholar 

  174. Pfeffer JM, Fischer TA, Pfeffer MA. 1995. Angiotensin-converting enzyme inhibition and ventricular remodeling after myocardial infarction. Ann Rev Physiol 57:805–826.

    Article  CAS  Google Scholar 

  175. Goldstein S, Sharov VG, Cook JM, Sabbah HN. 1995. Ventricular remodeling: Insights from pharmacologic interventions with angiotensin converting enzyme inhibitors. Mol Cell Biochem 147:51–55.

    Article  PubMed  CAS  Google Scholar 

  176. Kramer CM, Ferrari VA, Rogers WJ, Theobald TM, Nance LM, Axel L, Reichek A. 1996. Angiotensin-converting enzyme inhibition limits dysfunction in adjacent noninfarcted regions during left ventricular remodeling. J Am Coll Cardiol 27:211–217.

    Article  PubMed  CAS  Google Scholar 

  177. Dixon IMC, Ju H, Jassal DS, Peterson DJ. 1996. Effect of ramipril and losartan on collagen expression in right and left heart after myocardial infarction. Mol Cell Biochem 165:31–45.

    Article  PubMed  CAS  Google Scholar 

  178. Gaballa MA, Raya T, Goldman S. 1995. Large artery remodeling after myocardial infarction. Am J Physiol 268:H2092–H2103.

    PubMed  CAS  Google Scholar 

  179. Ball SG, Hall AS, Murray GD. 1995. Angiotensin-converting enzyme inhibitors after myocardial infarction: Indications and timing. J Am Coll Cardiol 25(Suppl 7):42S–46S.

    Article  PubMed  CAS  Google Scholar 

  180. van Gilst WH, Kingma JH, Peels KH, Dambrink JHE, Sutton MSJ. 1996. Which patient benefits from early angiotensin-converting enzyme inhibition after myocardial infarction? Results of one-year serial echocardiographic following from the captopril and thrombolysis study (CATS). J Am Coll Cardiol 28:114–121.

    Article  PubMed  Google Scholar 

  181. Schoemaker RG, Debets JJM, Struyker-Boudier HAJ, Smits JFM. 1991. Delayed but not immediate captopril therapy improves cardiac function in conscious rats following myocardial infarction. J Mol Cell Cardiol 23:187–197.

    Article  PubMed  CAS  Google Scholar 

  182. Cleland JGF, Poole-Wilson PA. 1994. ACE inhibitors for heart failure: A question of dose. Br Heart J 72(Suppl 3): 106–110.

    Article  Google Scholar 

  183. Wollert KC, Studer R, von Bülow B, Drexler H. 1994. Survival after myocardial infarction in the rat. Role of tissue angiotensin-converting enzyme inhibition. Circulation 90:2457–2467.

    Article  PubMed  CAS  Google Scholar 

  184. Perich RB, Jackson B, Rogerson F, Mendelsohn FAO, Paxton D, Johnston CL. 1992. Two binding sites on angiotensin I-converting enzyme: Evidence from radioligand binding studies. Mol Pharmacol 42:286–293.

    PubMed  CAS  Google Scholar 

  185. Dell’Italia LJ, Oparil S. 1996. Cardiac renin angiotensin system in hypertrophy and the progression to heart failure. Heart Failure Reviews 1:63–72.

    Article  Google Scholar 

  186. Garcia R, Qing G. 1993. Characterization of plasma and tissue atrial natriuretic factor during development of moderate high output heart failure in the rat. Circ Res 27:464–470.

    Google Scholar 

  187. Winkins MR, Settle SL, Stockmann PT, Needleman P. 1990. Maximizing the natriuretic effect of endogenous atriopeptin in a rat model of heart failure. Proc Natl Acad Sci USA 87:6465–6469.

    Article  Google Scholar 

  188. Arnal JF, Philippe M, Laboulandine I, Michel JB. 1993. Effect of perindopril in rat cardiac volume overload. Am Heart J 126:776–782.

    Article  PubMed  CAS  Google Scholar 

  189. Takeda N, Tanamura A, Iwai T, Kato M, Noma K, Nagano M. 1993. Beneficial effect of ACE inhibitor in congestive heart failure. Mol Cell Biochem 129:139–143.

    Article  PubMed  CAS  Google Scholar 

  190. Ruzicka M, Yuan B, Harmsen E, Leenen FHH. 1993. The renin-angiotensin system and volume overload-induced cardiac hypertrophy in rats: Effects of angiotensin converting enzyme inhibitor versus Ang II receptor blocker. Circulation 87:921–930.

    Article  PubMed  CAS  Google Scholar 

  191. Ruzicka M, Yuan B, Leenen FHH. 1994. Effects of enalapril versus losartan on regression of volume overload-induced cardiac hypertrophy in rats. Circulation 90:484–491.

    Article  PubMed  CAS  Google Scholar 

  192. Garcia R, Bonhomme MC, Diebold S. 1994. Captopril treatment does not restore either the renal or the ANF release response during volume expansion in moderate to severe high output heart failure. Cardiovasc Res 28:1533–1539.

    Article  PubMed  CAS  Google Scholar 

  193. Ruzicka M, Keeley FW, Leenen FHH. 1994. The renin-angiotensin system and volume overload-induced changes in cardiac collagen and elastin. Circulation 90:1989–1996.

    Article  PubMed  CAS  Google Scholar 

  194. Ruzicka M, Leenen FHH. 1995. Relevance of blockade of cardiac and circulatory angiotensin-converting enzyme for the prevention of volume overload-induced cardiac hypertrophy. Circulation 91:16–19.

    Article  PubMed  CAS  Google Scholar 

  195. Ruzicka M, Sharda V, Leenen FHH. 1995. Effects of ACE inhibitors on circulating versus cardiac angiotensin II in volume overload induced cardiac hypertrophy in rats. Circulation 92:3568–3573.

    Article  PubMed  CAS  Google Scholar 

  196. Feldman AM, Weinberg EO, Ray PH, Lorell BH. 1993. Selective changes in cardiac gene expression during compensated hypertrophy and the transition to cardiac decompensation in rats with chronic aortic banding. Circ Res 73:184–192.

    Article  PubMed  CAS  Google Scholar 

  197. Baker KM, Chernin MI, Wixson SK, Aceto JF. 1990. Renin angiotensin system involvement in pressure-overload cardiac hypertrophy in rats. Am J Physiol 259.H324–H332.

    PubMed  CAS  Google Scholar 

  198. Kromer EP, Riegger GAJ. 1988. Effects of long-term angiotensin converting enzyme inhibition on myocardial hypertrophy in experimental aortic stenosis in the rat. Am J Cardiol 62:161–163.

    Article  PubMed  CAS  Google Scholar 

  199. Linz W, Scholkens BA, Ganten D. 1989. Converting enzyme inhibition specifically prevents the development and induced regression of cardiac hypertrophy in rats. Clin Exp Hypertens 11A: 1325–1350.

    Article  Google Scholar 

  200. Weinberg EO, Schoen FJ, George D, Kagaya Y, Douglas PS, Litwin SE, Schunkert H, Benedict CR, Lorell BH. 1994. Angiotensin-converting enzyme inhibition prolongs survival and modifies the transition to heart failure in rats with pressure overload hypertrophy due to ascending aortic stenosis. Circulation 90:1410–1422.

    Article  PubMed  CAS  Google Scholar 

  201. Litwin SE, Katz SE, Weinberg EO, Lorell BH, Aurigemmma GP, Douglas PS. 1995. Serial echocardiographic-Doppler assessment of left ventricular geometry and function in rats with pressure-overload hypertrophy: Chronic angiotensin-converting enzyme inhibition attenuated the transition to heart failure. Circulation 91:2642–2654.

    Article  PubMed  CAS  Google Scholar 

  202. Mohabir R, Young SD, Strosberg AM. 1994. Role of angiotensin in pressure overload-induced hypertrophy in rats: Effects of angiotensin-converting enzyme inhibitors, an AT1 receptor antagonist, and surgical reversal. J Cardiol Pharmacol 23:291–299.

    Article  CAS  Google Scholar 

  203. Spinale FG, Holzgrefe HH, Mukherjee R, Hird RB, Walker JD, Arnim-Barker A, Powell JR, Koster WH. 1995. Angiotensin-converting enzyme inhibition and the progression of congestive cardiomyopathy: Effects of left ventricular and myocyte structure and function. Circulation 92:562–578.

    Article  PubMed  CAS  Google Scholar 

  204. Ogilvie RI, Zborowska-Sluis D. 1993. Captopril attenuates pacing-induced acute heart failure by increasing total vascular capacitance. J Cardiol Pharmacol 22:153–159.

    Article  CAS  Google Scholar 

  205. Hirakata H, Fouad-Trazi FM, Bumpus FM, Khosla M, Healy B, Husain A, Urata H, Kumagai H. 1990. Angiotensin and the failing heart: Enhanced positive inotropic response to angiotensin I in cardiomyopathic hamster heart in the presence of captopril. Circ Res 66:891–899.

    Article  PubMed  CAS  Google Scholar 

  206. Masutomo K, Makino N, Matuyama T, Shimada T, Yanaga T. 1996. Effects of enalapril on the collagen matrix in cardiomyopathic Syrian hamsters (BIO 14.6 and 53.58). Jpn Circ J 60:50–61.

    Article  PubMed  CAS  Google Scholar 

  207. Chopra M, Scott N, McMurray J, McLay J, Bridges A, Smith WE, Belch JJF. 1989. Captopril: A free radical scavenger. Br J Clin Pharmacol 27:396–399.

    Article  PubMed  CAS  Google Scholar 

  208. Bagchi D, Prasad R, Das DK. 1989. Direct scavenging of free radical by captopril, an angiotensin converting enzyme inhibitor. Biochem Biophys Res Comm 158:52–57.

    Article  PubMed  CAS  Google Scholar 

  209. Ziehut W, Studer R, Laurent D, Kästner S, Allegrini P, Whitebread S, Cumin F, Baum HP, de Gsparo M, Drexler H. 1996. Left ventricular wall stress and sarcoplasmic reticulum Ca2+-ATPase gene expression in renal hypertensive rats: Dose-dependent effects of ACE inhibition and AT1-receptor blockade. Cardiovasc Res 31:758–768.

    Google Scholar 

  210. Kagaya Y, Hajjar RJ, Gwathmey JK, Barry WH, Lorell BH. 1996. Long-term angiotensin-converting enzyme inhibition with fosinopril improves depressed responsiveness to Ca in myocytes from aortic-banded rats. Circulation 94:2951-2922.

    Google Scholar 

  211. Sanshi A, Takeo S. 1995. Long-term treatment with angiotensin I-converting enzyme inhibitors attenuates the loss of cardiac β-adrenoceptor responses in rats with chronic heart failure. Circulation 92:2666–2675.

    Article  Google Scholar 

  212. Linz W, Schökens BA. 1992. Role of bradykinin in the cardiac effects of angiotensin-converting enzyme inhibitors. J Cardiovasc Pharmacol 20(Suppl IX):S81–S90.

    Google Scholar 

  213. Linz W, Wiemer G, Schaper J, Zimmermann R, Nagasawa K, Gohlke P, Unger T, Schölkens BA. 1995. Angiotensin converting enzyme inhibitors, left ventricular hypertrophy and fibrosis. Mol Cell Biochem 147:89–97.

    Article  PubMed  CAS  Google Scholar 

  214. Waeber B, Brunner HR. 1996. Cardiovascular hypertrophy: Role of Ang II and bradykinin. J Cardiol Pharmacol 27(Suppl 2):S36–S40.

    Article  CAS  Google Scholar 

  215. Gohike P, Linz W, Schölkens BA, Kuwer I, Bartenbach S, Schnell A, Unger T. 1994. Angiotensin-converting enzyme inhibition improves cardiac function: Role of bradykinin. Hypertension 23:411–418.

    Article  Google Scholar 

  216. Zhu P, Zaugg CE, Simper D, Hornstein P, Allegrini PR, Buser PT. 1995. Bradykinin improves postischemic recovery in the rat heart: role of high energy phosphates, nitric oxide, and prostacyclin. Cardiovasc Res 29:658–663.

    PubMed  CAS  Google Scholar 

  217. Lambert F, Lecarpentier Y, Lompré AM, Sealbert E, Desché P, Chemla D. 1995. Relations between myocardial contractility, myosin phenotype, and plasma angiotensin-converting enzyme activity in the cardiomyopathic hamster. J Cardiovasc Pharmacol 25:410–415.

    Article  PubMed  CAS  Google Scholar 

  218. Michel JB, Lattion AL, Salzmann JL, Cerol M de L, Philippe M, Camilleri JP, Corvol P. 1988. Hormonal and cardiac effects of converting enzyme inhibition in rat myocardial infarction. Circ Res 62:641–650.

    Article  PubMed  CAS  Google Scholar 

  219. Osterziel KJ, Dietz R. 1996. Improvement of vagal tone by ACE inhibition: A mechanism of cardioprotection in patients with mild to moderate heart failure. J Cardiovasc Pharmacol 27(Suppl 2):S25–S30.

    Article  PubMed  CAS  Google Scholar 

  220. Marakas SA, Kyriakidis K, Vourlioti N, Petropoulakis PN, Toutoizas PK. 1995. Acute effect of captopril administration on baroreflex sensitivity in patients with acute myocardial infarction. Eur Heart J 16:914–921.

    PubMed  CAS  Google Scholar 

  221. Lang CC, Stein CM, He HB, Wood AJJ. 1996. Angiotensin converting enzyme inhibition and sympathetic activity in healthy subjects. Clin Pharmacol Ther 59:668–674.

    Article  PubMed  CAS  Google Scholar 

  222. Schultheiss HP, Ullrich G, Schindler M, Schulze K, Strauer BE. 1990. The effect of ACE inhibition on myocardial energy metabolism. Eur Heart J 11(Suppl B): 116–122.

    Article  PubMed  CAS  Google Scholar 

  223. Ishikawa K, Hashimoto H, Mitani S, Toki Y, Okumura K, Ito T. 1995. Enalapril improves heart failure by monocrotaline without reducing pulmonary hypertension in rats: Role of preserved myocardial creatine kinase and lactate dehydrogenase isoenzymes. Int J Cardiol 47:225–233.

    Article  PubMed  CAS  Google Scholar 

  224. Zhang X, Xie YW, Nasjletti A, Xu X, Wolin MS, Hintze TH. 1997. ACE inhibitor promotes nitric oxide accumulation to modulate myocardial oxygen consumption. Circulation 95:176–182.

    Article  PubMed  Google Scholar 

  225. Pals DT, Mosucci FD, Sipos F, Denning GSJR. 1970. A specific competitive inhibitor of Ang II. Proc Natl Acad Sci USA 67:1624–1630.

    Article  Google Scholar 

  226. Chiu AT, McCall DE, Price WA, Wong PC, Carini DJ, Duncia JV. 1990. Non peptide Ang II receptor antagonists: VII. Cellular and biochemical pharmacology of DuP 753, an orally active antihypertensive agent. J Pharmacol Exp Ther 252:711–718.

    PubMed  CAS  Google Scholar 

  227. Wong PC, Price WA, Chiu AT, Duncia JV, Chrini DJ, Wexler RR. 1990. Nonpeptide Ang II receptor antagonists: VIII. Characterization of functional antagonism displayed by DuP 753, an orally active antihypertensive agent. J Pharmacol Exp Ther 252:719–725.

    PubMed  CAS  Google Scholar 

  228. Duncia JV, Carini DJ, Chiu AT, Johnson AL, Price WA, Wong PC, Wexler RR, Timmermans PBMWM. 1992. The discovery of DuP 753, a potent, orally active nonpeptide Ang II receptor antagonist. Med Res Rev 12:149–191.

    Article  PubMed  CAS  Google Scholar 

  229. Ji H, Leung M, Zhang Y, Catt KJ, Sandberg K. 1994. Differential structure requirements for specific binding of nonpeptide and peptide antagonists to the AT1 angiotensin receptor: Identification of amino acid residues that determine binding of the antihypertensive drug losartan. J Biol Chem 269:16533–16536.

    PubMed  CAS  Google Scholar 

  230. Raya TE, Fonken SJ, Lee RW, Daugherty S, Goldman S, Wong PC, Timmermans PBMWM, Morkin E. 1991. Hemodynamic effects of direct Ang II blockade compared to converting enzyme inhibition in rat model of heart failure. Am J Hypertens 4:334S–340S.

    PubMed  CAS  Google Scholar 

  231. Smits JFM, van Krimpen C, Schoemaker RG, Cleutjens JPM, Daemen MJAP. 1992. Ang II receptor blockade after myocardial infarction in rats: Effects of hemodynamics, myocardial DNA synthesis, and interstitial collagen content. J Cardiovasc Pharmacol 20:772–778.

    PubMed  CAS  Google Scholar 

  232. Gottlieb SS, Dickstein KD, Fleck E, Kostis J, Levine TB, Le Jemtel T, De Kock M. 1993. Hemodynamic and neurohormonal effects of the Ang II antagonist losartan in patients with congestive heart failure. Circulation 88:1602–1609.

    Article  PubMed  CAS  Google Scholar 

  233. Regitz-Zagrosek V, Neuss M, Holzmeister J, Fleck E. 1995. Use of Ang II antagonists in human heart failure: Function of the subtype 1 receptor. J Hypertens 13(Suppl 1):S63–S71.

    Article  CAS  Google Scholar 

  234. Crozier I, Ikram H, Awan N, Cleland J, Stephen N, Dickstein K, Frey M, Young J, Klinger G, Makris L, Rucinska E. For the losartan hemodynamic study group. 1995. Losartan in heart failure: Hemodynamic effects and tolerability. Circulation 91:691–697.

    Article  PubMed  CAS  Google Scholar 

  235. Cheng CP, Suzuki M, Ohte N, Ohno M, Wang ZM, Little WC. 1996. Altered ventricular and myocyte response to Ang II in pacing-induced heart failure. Circ Res 78:880–892.

    Article  PubMed  CAS  Google Scholar 

  236. Kojima M, Shiojima I, Yamazaki T, Komuro I, Zou Y, Wang Y, Mizuno T, Ueki K, Tobe K, Kadowaki T, Nagai R, Yazaki Y. 1994. Ang II receptor antagonist TCV-116 induces regression of hypertensive left ventricular hypertrophy in vivo and inhibits the intracellular signaling pathway of stretch-mediated cardiomyocyte hypertrophy in vitro. Circulation 89:2204–2211.

    Article  PubMed  CAS  Google Scholar 

  237. Hantani A, Yoshiyama M, Kim S, Omura T, Toda I, Akioka K, Teragaki M, Takeuchi K, Iwao H, Takeda T. 1995. Inhibition by Ang II type 1 receptor antagonist of cardiac phenotypic modulation after myocardial infarction. J Mol Cell Cardiol 27:1905–1914.

    Article  Google Scholar 

  238. Nishikimi T, Yamagishi H, Takeuchi K, Takeda T. 1995. An Ang II receptor antagonist attenuates left ventricular dilatation after myocardial infarction in the hypertensive rat. Cardiovasc Res 29:856–861.

    PubMed  CAS  Google Scholar 

  239. Rush JE, Rajfer SI. 1993. Theoretical basis for the use of Ang II antagonists in the treatment of heart failure. J Hypertens 11(Suppl 3):S69–S71.

    CAS  Google Scholar 

  240. Campbell DJ, Kladis A, Valentijn AJ. 1995. Effects of losartan on angiotensin and bradykinin peptides and angiotensin converting enzyme. J Cardiol Pharmacol 26:233–240.

    Article  CAS  Google Scholar 

  241. Dickstein K, Chang P, Willenheimer R, Haunsø S, Remes J, Hall C, Kjekshus J. 1995. Comparison of the effects of losartan and enalapril on clinical status and exercise performance in patients with moderate or severe chronic heart failure. J Am Coll Cardiol 26:438–445.

    Article  PubMed  CAS  Google Scholar 

  242. Eberhardt RT, Kevak RM, Kang PM, Frishman WH. 1993. Ang II receptor blockade: An innovative approach to cardiovascular pharmacotherapy. J Clin Pharmacol 33:1023–1038.

    Article  PubMed  CAS  Google Scholar 

  243. van Wijngaarden J, Pinto YM, van Gilst WH, de Graeff PA, de Langen CDJ, Wessling H. 1991. Conceiting enzyme inhibition after experimental myocardial infarction in rats: Comparative study between spirapril and zofenopril. Cardiovasc Res 25:936–942.

    Article  PubMed  Google Scholar 

  244. van Wijngaarden J, Monninlk SHJ, Bartels H, van Gilst WH, de Langen CDJ, Wessling H. 1992. Captopril modifies the response of infarcted rat hearts to isoprenaline stimulation. J Cardiovasc Pharmacol 19:741–747.

    PubMed  Google Scholar 

  245. Sweet CS, Emmert SE, Stabilito II, Ribeiro LGT. 1987. Increased survival in rats with congestive heart failure treated with enalapril. J Cardiovasc Pharmacol 10:636–642.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Canada

    Qiming Shao, Vincenzo Panagia, Robert E. Beamish & Naranjan S. Dhalla

  2. Department of Physiology, Faculty of Medicine University of Manitoba, Winnipeg, Canada

    Qiming Shao, Vincenzo Panagia, Robert E. Beamish & Naranjan S. Dhalla

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  1. Qiming Shao
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  2. Vincenzo Panagia
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  3. Robert E. Beamish
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  4. Naranjan S. Dhalla
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Editors and Affiliations

  1. Institute of Cardiovascular Sciences St. Boniface General Hospital Research Centre Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    Naranjan S. Dhalla Ph.D., M.D. (Hon.) (Distinguished Professor and Director MRC Group in Experimental Cardiology), Peter Zahradka Ph.D. (Associate Professor), Ian M. C. Dixon Ph.D. (Assistant Professor) & Robert E. Beamish M.D. (Professor Emeritus) (Distinguished Professor and Director MRC Group in Experimental Cardiology),  (Associate Professor),  (Assistant Professor) &  (Professor Emeritus)

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Shao, Q., Panagia, V., Beamish, R.E., Dhalla, N.S. (1998). Role of Renin-Angiotensin System in Cardiac Hypertrophy and Failure. In: Dhalla, N.S., Zahradka, P., Dixon, I.M.C., Beamish, R.E. (eds) Angiotensin II Receptor Blockade Physiological and Clinical Implications. Progress in Experimental Cardiology, vol 2. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5743-2_22

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  • DOI: https://doi.org/10.1007/978-1-4615-5743-2_22

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