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The Renin-Angiotensin System and the Heart

  • Chapter
Hormones and the Heart in Health and Disease

Part of the book series: Contemporary Endocrinology ((COE,volume 21))

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Abstract

The discovery of the renin-angiotensin system (RAS) opened a new era in the research of the physiology and pathology of the cardiovascular system. Early studies relying on measurements of plasma renin levels had raised doubts about the participation of the RAS in the development and maintenance of hypertension (HT), but these doubts were laid to rest when antagonists or inhibitors of various components of the system were used to demonstrate its role. Use of these antagonists/inhibitors also permitted the elucidation of various aspects of the contribution of the RAS to the onset and progression of ischemic cardiac disease through the successive stages of ischemia, myocardial infarcts, diastolic and systolic dysfunction, and congestive heart failure (CHF). The corollary of this research was the introduction of angiotensin inhibition in the treatment of HT, ischemic heart disease, and heart failure (HF).

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References

  1. Lee MR. Kinetics of renin-substrate reaction. In: Renin and Hypertension. Williams & Wilkins, Baltimore, MD, 1969, pp. 25–27.

    Google Scholar 

  2. Campbell DJ. Circulating and tissue angiotensin systems. J Clin Invest 1987; 79: 1–5.

    Article  PubMed  CAS  Google Scholar 

  3. Laragh JH. Extrarenal tissue prorenin systems do exist: are intrinsic vascular and cardiac tissue renins fact or fancy? Am J Hypertens 1989; 2: 262–265.

    PubMed  CAS  Google Scholar 

  4. Dostal DE, Baker KM. Evidence for a role of an intracardiac renin-angiotensin. Trends Cardiovasc Med 1993; 3: 67–74.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  7. Dzau VJ, Ellison EK, Brody T, Ingelfinger J, Pratt R. Comparison study of the distribution of renin and angiotensinogen messenger ribonucleic acids in rat and mouse tissues. Endocrinology 1987; 120: 2334–2338.

    Article  PubMed  CAS  Google Scholar 

  8. Hackenthal E, Paul M, Ganten D, Taugner R. Morphology, physiology, and molecular biology of renin secretion. Physiol Rev 1990; 70: 1067–1116.

    PubMed  CAS  Google Scholar 

  9. Dostal DE, Baker KM. Biochemistry, molecular biology, and potential roles of the cardiac reninangiotensin system. In: Dhalla NS, Takeda N, Nagano M, eds. The Failing Heart. Lippincott-Raven, Philadelphia, PA, 1995, pp. 275–294.

    Google Scholar 

  10. Rogers TB, Gaa ST, Allen IS. Identification and characterization of functional angiotensin II receptors on cultured heart myocytes. J Pharm Exp Ther 1986; 236: 438–444.

    CAS  Google Scholar 

  11. Allen IS, Cohen NM, Dhallan RS, Gaa ST, Lederer WJ, Rogers TB. Angiotensin II increases spontaneous contractile frequency and stimulates calcium current in cultured neonatal rat heart myocytes: insights into the underlying biochemical mechanisms. Circ Res 1988; 62: 524–534.

    Article  PubMed  CAS  Google Scholar 

  12. Urata H. Healy B, Stewart RW, Bumpus FM, Husain A. Angiotensin receptors in normal and failing human hearts. J Clin Endocrinol Metab 1989; 69: 54–66.

    Article  PubMed  CAS  Google Scholar 

  13. Lopez JJ, Lorell BH, Ingelfinger JR, Weinberg EO, Schunkert H, Diamant D, Tang S-S. Distribution and function of cardiac angiotensin ATl and AT2 receptor subtypes in hypertrophied rat hearts. Am J Physiol 1994; 267: H844 - H852.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  15. Liu Y-H, Yang X-P, Sharov VG, Nass O, Sabbah HN, Peterson E, Carretero OA. 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. J Clin Invest 1997; 99: 1926–1935.

    Article  PubMed  CAS  Google Scholar 

  16. Levy D, Garrison RJ, Savage DD, Kannel WB, Castelli WP. Left ventricular mass and incidence of coronary heart disease in an elderly cohort; the Framingham Heart Study. Ann Intern Med 1989; 110: 101–107.

    PubMed  CAS  Google Scholar 

  17. Stouffer GA, Owens GK. Angiotensin II-induced mitogenesis of spontaneously hypertensive rat-derived cultured smooth muscle cells is dependent on autocrine production of transforming growth factor-beta. Circ Res 1992; 70: 820–828.

    Article  PubMed  CAS  Google Scholar 

  18. Naftilan Ai, Pratt RE, Dzau VJ. Induction of plaelet-derived growth factor A-chain and c-myc gene expression by angiotenin II in cultured rat vascular smooth muscle cells. J Clin Invest 1989; 83: 1419–1424.

    Article  PubMed  CAS  Google Scholar 

  19. Schorb W, Singer HA, Dostal DE, Baker KM. Angiotensin II is a potent simulator of MAP-kinase activity in neonatal rat cardiac fibroblasts. J Mol Cell Cardiol 1995; 27: 1151–1160.

    Article  PubMed  CAS  Google Scholar 

  20. Delafontaine P, Lou H. Angiotensin II regulates insulin-like growth factor I gene expression in vascular smoth muscle cells. J Biol Chem 1993; 268: 16, 866–16, 870.

    Google Scholar 

  21. Naftilan AJ, Pratt RE, Eldrige CS, Lin HL, Dzau VJ. Angiotensin II induces c-fos expression in smooth muscle via transcriptional control. Hypertension 1989; 13: 706–711.

    Article  PubMed  CAS  Google Scholar 

  22. Pauet J-L, Baudouin-Legros M, Brunell G, Meyer P. Angiotensin II-induced proliferation of aortic myocytes in spontaneously hypertensive rats. J Hypertens 1990; 8: 565–572.

    Article  Google Scholar 

  23. Yu C, Tsai M, Stacey DW. Cellular ras activity and phospholipid metabolism. Cell 1988; 52: 63–71.

    Article  PubMed  CAS  Google Scholar 

  24. Knauss TC, Jaffer FE, Abboud HE. Phosphatidic acid modulates DNA synthesis, phospholipase C, and platelet-derived growth factor mRNAs in cultured mesangial cells. J Biol Chem 1990; 265: 14, 457–14, 463.

    Google Scholar 

  25. Moolenaar WH, Kruijer W, Till BC, Verlaan I, Bierman AJ, deLaat SW. Growth factor-like action of phosphatidic acid. Nature 1991; 323: 171–173.

    Article  Google Scholar 

  26. Khairallah PA, Robertson AL, Davila D. Effect of angiotensin II on DNA, RNA, and protein synthesis. In: Genest J, Koiw E, eds. Hypertension. Springer Verlag, New York, 1972, pp. 212–220.

    Google Scholar 

  27. Nakajima M, Hutchinson HG, Fujinaga W, Hayashida R, Morishita L, Zhang Horiuchi M, Pratt RE, Dzau VJ. Angiotensin II type 2 (AT2) receptor antagonizes the growth effects of the AT receptor: gainof-function study using gene transfer. Proc Natl Acad Sci USA 1995; 92: 10, 663–10, 667.

    Google Scholar 

  28. Stoll M, Steckelings UM, Paul M, Bottari SP, Metzger R, Unger T. Angiotensin AT2-receptor mediates inhibition of cell proliferation in coronary endothelial cells. J Clin Invest 1995; 95: 651–657.

    Article  PubMed  CAS  Google Scholar 

  29. Newling RP, Fletcher Pi, Coutis M, Shaw J. Noradrenaline and cardiac hypertrophy in the rat: changes in morphology, blood pressure and ventricular performance. J Hypertens 1989; 7: 561–567.

    CAS  Google Scholar 

  30. Imai T, Hirata Y, Emori T, Yanagisawa M, Masaki T, Marumo F. Induction of endothelin-1 gene by angiotensin and vasopressin in endothelial cells. Hypertension 1992; 19: 753–757.

    Article  PubMed  CAS  Google Scholar 

  31. Chua BH, Chua CC, Diglio CA, Siu BB. Regulation of endothelin-1 mRNA by angiotensin II in rat heart endothelial cells. Biochim Biophys Acta 1993; 1178: 201–206.

    Article  PubMed  CAS  Google Scholar 

  32. Sung CP, Arleth AJ, Storer BL, Ohlstein EH. Angiotensin type 1 receptors mediate smooth muscle proliferation and endothelin biosynthesis in rat vascular smooth muscle. J Pharmacol Exp Ther 1994; 271: 429–437.

    Google Scholar 

  33. Ito H, Hirata Y, Adachi S, Tanaka M, Tsujino M, Koike A, et al. Endothelin-1 is an autocrine/paracrine factor in the mechanism of angiotensin II-induced hypertrophy in cultured rat cardiomyocytes. J Clin Invest 1993; 92: 398–403.

    Article  PubMed  CAS  Google Scholar 

  34. Yamazaki T, Tobe K, Hoh E, Maemura K, Kaida T, Komuro H. Mechanical loading activates mitogenactivated protein kinase and S6 peptide kinase in cultured rat cardiac myocytes. J Biol Chem 1993; 268: 12, 069–12, 076.

    Google Scholar 

  35. Komuro I, Katoh Y, Kaida T, Shibazaki Y, Kurabayashi M. Mechanical loading stimulates cell hypertrophy and specific gene expression in cultured rat cardiac myocytes. J Biol Chem 1991; 266: 1265–1268.

    PubMed  CAS  Google Scholar 

  36. Lindpaintner K, Ganten D. The cardiac renin-angiotensin system. Circ Res 1991; 68: 905–921.

    Article  PubMed  CAS  Google Scholar 

  37. Fabris B, Jackson B, Kohzuki M, Perich R, Johnston CI. Increased cardiac angiotensin-converting enzyme in rats with chronic heart failure. Clin Exp Pharmacol Physiol 1990; 17: 309–314.

    Article  PubMed  CAS  Google Scholar 

  38. Scott-Burden T, Hahn AWA, Resink TJ, Buhler FR. Modulation of extracellular matrix by angiotensin II: stimulated glycoconjugate synthesis and growth in vascular smooth muscle cells. J Cardiovasc Pharmacol 1990; 16 (Suppl 4): 36–41.

    Article  Google Scholar 

  39. Vogin EE, Buckley JP. Cadiac effects of angiotensin II. J Pharmacol Sci 1964; 53: 1482–1486.

    Article  CAS  Google Scholar 

  40. Kobayashi M, Furukawa Y, Chiba S. Positive chronotropic and inotropic effects of angiotensin II in the dog heart. Eur J Pharmacol 1978; 50: 17–25.

    Article  PubMed  CAS  Google Scholar 

  41. Malik KU, Nasjletti A. (1976) Facilitation of adrenergic transmission by locally generated angiotensin II in rat mesenteric arteries. Circ Res 38: 26–30.

    Article  PubMed  CAS  Google Scholar 

  42. Carlsson L, Abrahamsson T. Ramiprilat attenuates the local release of noradrenaline in the ichemic myocardium. Eur J Pharmacol 1989; 166: 157–164.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  44. Foult JM, Travalaro O, Autony I, Nittenberg A. Direct myocardial and coronary effects of enalaprilat in patient with dilated cardiomyopathy: assessment by a bilateral intracoronary infusion technique. Circulation 1988; 77: 337–344.

    Article  PubMed  CAS  Google Scholar 

  45. Saito K, Gutkind JS, Saavedra JM. Angiotensin II binding sites in the conduction system of rat hearts. Am J Physiol 1987; 253: H1618 - H1622.

    PubMed  CAS  Google Scholar 

  46. Kass RS, Blair ML. Effects of angiotensin II on membrane current in cardiac Purkinje fibers. J Mol Cell Cardiol 1981; 13: 797–809.

    Article  PubMed  CAS  Google Scholar 

  47. De Mello WC. Renin-angiotensin system and cell communication in the failing heart. Hypertension 1996; 27: 1267–1272.

    Article  PubMed  Google Scholar 

  48. De Mello WC. Is an intracellular renin-angiotensin system involved in control of cell communication in heart? J Cardiovasc Pharmacol 1994; 23: 640–646.

    Article  PubMed  Google Scholar 

  49. De Mello WC, Crespo MJ. Cardiac refractoriness in rats is reduced by angiotensin II. J Cardiovasc Pharmacol 1995; 25: 51–56.

    Article  PubMed  Google Scholar 

  50. Dosemeci A, Dhallan RS, Cohen NM, Lederer WJ, Rogers TB. Phorbol ester increases calcium current and stimulates the effects of angiotensin II on cultured neonatal rat heart myocytes. Circ Res 1988; 62: 347–357.

    Article  PubMed  CAS  Google Scholar 

  51. Rajagopalan S, Laursen JB, Borthayre A, Kurz S, Keiser J, Haleen S, Giaid A, Harrison DG. Role for endothelin-1 in angiotensin II-mediated hypertension. Hypertension 1997; 30 (Part 1): 29–34.

    Article  PubMed  CAS  Google Scholar 

  52. Starke K. Action of angiotensin on uptake, release, and metabolism of 14C NE by isolated rabbit hearts. Eur J Pharmacol 1971; 14: 112–123.

    Article  PubMed  CAS  Google Scholar 

  53. Aiken JW, Reit E. Stimulation of the cat stellate ganglion by angiotensin. J Pharmacol Exp Ther 1968; 159: 107–114.

    Google Scholar 

  54. Lee WB, Ismay MJ, Lumbers ER. Mechanisms by which angiotensin affects the heart rate of the conscious sheep. Circ Res 1980; 47: 286–292.

    Article  PubMed  CAS  Google Scholar 

  55. Ponikowski P, Auker SD, Amadi A, Chua TP, Cerquetain D, Ondusova D, et al. Heart rhythms, ventricular arrhythmias and death in chronic heart failure. J Cardiac Failure 1996; 2: 1772–1783.

    Article  Google Scholar 

  56. De Mello WC, Crespo MJ, Altieri PI. Enalapril increases cardiac refractoriness. J Cardiovasc Pharmacol 1992; 20: 820–825.

    PubMed  Google Scholar 

  57. Kingma JH, De Graeff PA, Van Guist WH, van Binsbergen E, de Langen CDJ, Wesseling H. Effects of intravenous captopril on inducible sustained ventricular tachycardia. Postgrad Med 1986; 62: 159–163.

    Article  Google Scholar 

  58. Wesseling H, De Graeff PA, Van Gilst WH, Kingma JH, de Langen CDJ. Cardiac arrhythmias: a new indication for angiotensin converting enzyme inhibitors. J Hum Hypertens 1989; 3: 89–95.

    PubMed  Google Scholar 

  59. Van Gilst WH, De Graeff PA, Wesseling H, de Langen CDJ. Reduction of reperfusion arrhythmias in the ischemic isolated rat heart by angiotensin converting enzyme inhibitors: a comparison of captopril, enalapril, and HOE498. J Cardiovasc Pharmacol 1986; 8: 722–728.

    PubMed  Google Scholar 

  60. Pitt B, Segal R, Martinez FA, Meurers G, Cowley AJ, Thomas I. Randomized trial of losartan versus captopril in patients over 65 with heart failure (Evaluation of losartan in the Elderly Study, ELITE). Lancet 1997; 349: 747–752.

    Article  PubMed  CAS  Google Scholar 

  61. Ridker PM. Epidemiologic assessment of thrombotic risk factors for cardiovascular disease. Cuff Opin Lipid 1992; 3: 285–290.

    Article  Google Scholar 

  62. Olson JA Jr, Ogilvie S, Buhi WC, Raizata MK. Angiotensin II induces secretion of plasminogen activator inhibitor I and a tissue metallopeptidase inhibitor-related protein from rat brain astrocytes. Neurobiology 1991; 88: 1928–1932.

    CAS  Google Scholar 

  63. Van Leeuwen RT, Kol A, Andreotti F, Kluft C, Maseri A, Sperti G. Angiotensin II increases plasminogen activator inhibitor type 1 and tissue-type plasminogen activator messenger RNA in culture rat aortic smooth muscle cells. Circulation 1994; 62: 362–368.

    Article  Google Scholar 

  64. Vaughn DE. Lazos SA, Tong K. Angiotensin II regulates the expression of plasminogen activator inhibitor-1 in cultured endothelial cells. A potential link between the renin-angiotensin system and thrombosis. J Clin Invest 1995; 95: 995–1001.

    Google Scholar 

  65. Ridker PM, Gaboury CL, Conlin PR, Seely EW, Williams GH, Vaughan DE. Stimulation of plasminogen activator inhibitor in vivo by infusion of angiotensin II. Evidence of a potential interaction between the renin-angiotensin system and fibrinolytic function. Circulation 1993; 87: 1969–1973.

    Article  PubMed  CAS  Google Scholar 

  66. Hamsten A, DeFaire U, Walldius G, Dahlen G, Szamosi A, Landou C, Blomback M, Wiman B. Plasminogen activator inhibitor in plasma: risk factor for recurrent myocardial infarction. Lancet 1987; 2: 3–9.

    Article  PubMed  CAS  Google Scholar 

  67. Pfeffer MA, Braunwald E, Moye LA, Basta L, Brown EJ, Cuddy TE, et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 1992; 327: 669–677.

    Article  PubMed  CAS  Google Scholar 

  68. Yusuf S, Pepine FJ. Garces C, Pouleur H, Salem D, Kostis J, et al. Effect of enalapril on myocardial infarction and unstable angina in patients with low ejection fractions. Lancet 1992; 340: 1173–1178.

    Article  PubMed  CAS  Google Scholar 

  69. Wright RA, Flapan AD, Alberti GMM, Ludlam CA, Fox AAA. Effects of captopril therapy on endogenous fibrinolysis in men with recent, uncomplicated myocardial infarction. J Am Coll Cardiol 1994; 24: 67–73.

    Google Scholar 

  70. Kerins DM, Hao Q, Vaughan DE. Angiotensin induction of PAI-1 expression in endothelial cells is mediated by the hexapeptide angiotensin IV. J Clin Invest 1995; 96: 2515–2520.

    Article  PubMed  CAS  Google Scholar 

  71. Gavras H. Angiotensin-converting enzyme inhibition and the heart. Hypertension 1994; 23: 813–818.

    Article  PubMed  CAS  Google Scholar 

  72. Gavras I. Bradykinin-mediated effects of ACE inhibition. Kidney Int 1992; 42: 1020–1029.

    Article  PubMed  CAS  Google Scholar 

  73. Oskarsson HJ, Heistad DD. Oxidative stress produced by angiotensin II: Implications for hypertension and vascular injury. Circulation 1997; 95: 557–559.

    Article  PubMed  CAS  Google Scholar 

  74. Griendling KK, Minieri CA, 011erenshaw JD, Alexander RW. Angiotensin II stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells. Circ Res 1994; 74: 1141–1148.

    Article  PubMed  CAS  Google Scholar 

  75. Ames BN, Shigenaga MK, Hagen TM. Oxidants, antioxidants, and the degenerative disease of aging. Proc Natl Acad Sci USA 1993; 90: 7915–7922.

    Article  PubMed  CAS  Google Scholar 

  76. Rajagopalan S, Kurz S, Munzel T, Tarpey M, Freeman BA, Griendling KK, Harrison DG. 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: 1916–1923.

    Article  PubMed  CAS  Google Scholar 

  77. Bech LJ, Rajagopalan S, Galis Z, Tarpey M, Freeman BA, Harrison DG. Role of superoxide in angiotensin II-induced but not catecholamine-induced hypertension. Circulation 1997; 95: 588–593.

    Article  Google Scholar 

  78. Katusic ZS, Vanhoutte PM. Superoxide anion is an endothelium-derived contracting factor. Am J Physiol 1989; 257: H33 - H37.

    PubMed  CAS  Google Scholar 

  79. McAlpine HM, Cobbe SM. Neuroendocrine changes in acute myocardial infarction. Am J Med 1988; 84(Suppl 3A ): 61–66.

    Google Scholar 

  80. Rouleau JL, Moye LA, de Champlain J, Klein M, Bichet D, Packer M, et al. Activation of neurohumoral systems following acute myocardial infarction. Am J Cardiol 1991; 68: 80D - 86D.

    Article  PubMed  CAS  Google Scholar 

  81. Braunwald E, Kloner RA. Myocardial reperfusion: a double-edged sword? J Clin Invest 1986; 76: 1713–1719.

    Article  Google Scholar 

  82. Li K, Chen X. Protective effects of captopril and enalapril on myocardial ischemia and reperfusion damage of rat. J Mol Cell Cardiol 1987; 19: 909–915.

    Article  PubMed  CAS  Google Scholar 

  83. Tio RA, De Langen CDJ, De Graeff PA, Van Gilst WH, Bel KJ, Wolters KGTP, et al. The effects of oral pretreatment with zofenopril an angiotensin-converting enzyme inhibitor, on early reperfusion and subsequent electrophysiologic stability in the pig. Cardiovasc Drugs Ther 1990; 4: 695–704.

    Article  PubMed  CAS  Google Scholar 

  84. Frei B. Reactive oxygen species and antioxidant vitamins Mechanisms of action. Am J Med 1994; 97(Suppl 3A ): 5–13.

    Google Scholar 

  85. Keaney JF, Frei B. Antioxidant protection of low-density lipoprotein and its role in the prevention of atherosclerotic vascular disease. In: Frei B, ed. Natural Antioxidants in Human Health and Disease. Orlando, Academic, 1994, pp. 303–351.

    Google Scholar 

  86. Keidar S, Kaplan M, Shapira C, Brook JG, Avirom M. Low density lipoprotein isolated from patients with essential hypertension exhibits increased propensity for oxidation and enhanced uptake by macrophages: a possible role for angiotensin II. Atherosclerosis 1994; 107: 71–84.

    Article  PubMed  CAS  Google Scholar 

  87. Marui N, Offermann MK, Swerlick R, Kunsch C, Rosen CA, Ahmad M, Alexander RW, Medford RM. Vascular cell adhesion molecule-1(VCAM-1) gene transcription and expression are regulated through an antioxidant-sensitive mechanism in human vascular endothelial cell. J Clin Invest 1993; 92: 1866–1874.

    Article  PubMed  CAS  Google Scholar 

  88. Fraticelli A, Serrano CV Jr Bochner BS, Capogrossi MC, Zweier JL. Hydrogen peroxide and superoxide modulate leukocyte adhesion molecule expression and leukocyte endothelial adhesion. Biochim Biophys Acta 1996; 1310: 251–259.

    Article  PubMed  Google Scholar 

  89. Puri PL, Avantaggiati ML, Burgio VL. Chirillo P, Collepardo D, Natoli G, Balsano C, Levrero M. Reactive oxygen intermediates mediate angiotensin II-induced c-jun c-fos heterodimer DNA binding activity and proliferative hypertropic responses in myogenic cells. J Biol Chem 1995; 270: 22, 129–22, 134.

    Google Scholar 

  90. Brunner HR, Laragh JR, Baer L, Newton MA, Goodwin FT, Krakoff LR, Bard RM, Buhler FR. Essential hypertension: renin and aldosterone, heart attack and stroke. N Engl J Med 1972; 286: 441–449.

    Article  PubMed  CAS  Google Scholar 

  91. Alderman MH, Madhavan S, Ooi WL, Cohen H, Sealey JE, Laragh JH. Association of the reninsodium profile with the risk of myocardial infarction in patients with hypertension. N Engl J Med 1991; 324: 10, 098–10104.

    Google Scholar 

  92. MacMahon SW, Cutler JA, Furberg CD, Payne GH. The effects of drug treatment for hypertension on morbidity and mortality from cardiovascular disease: a review of randomized controlled trials. Prog Cardiovasc Dis 1986; 29 (Suppl 1): 99–118.

    Article  PubMed  CAS  Google Scholar 

  93. Chobanian AV, Haudenschild CC, Nickerson C, Drago R. Antiatherogenic effect of captopril in the Watanabe heritable hyperlipidemic rabbit. Hypertension 1990; 15: 327–333.

    Article  PubMed  CAS  Google Scholar 

  94. Gavras H, Brown JJ, Lever AF, MacAdam RF, Robertson JIS. Acute renal failure, tubular necrosis and myocardial infarction induced in the rabbit by intravenous angiotensin II. Lancet 1971; II: 19–22.

    Article  Google Scholar 

  95. Gavras H, Kremer D, Brown JJ, Gray V, Lever AF, Macadam RF, et al. Angiotensin and norepinephrine-induced myocardial lesions: experimental and clinical studies in rabbit and man. Am Heart J 1975; 89: 321–332.

    Google Scholar 

  96. Gavras H, Liang C, Brunner HR. Redistribution of regional blood flow after inhibition of the angiotensin converting enzyme. Circ Res 1978; 43 (Suppl 1): 59–63.

    CAS  Google Scholar 

  97. Liang C, Gavras H, Hood WB Jr. Renin-angiotensin system inhibition in conscious sodium-depleted dogs: effects on systemic and coronary hemodynamics. J Clin Invest 1978; 61: 874–883.

    Article  PubMed  CAS  Google Scholar 

  98. Tan LB, Jalil JE, Pick R, Janicki JS, Weber KT. Cardiac myocyte necrosis induced by angiotensin II. Circ Res 1991; 69: 1185–1195.

    Article  PubMed  CAS  Google Scholar 

  99. Weber KT, Brilla CG, Campbell SE, Reddy HK. Myocardial fibrosis and the concepts of cardioprotection and cardioreparation. J Hypertens 1992; 10 (Suppl 5): S87 - S94.

    Article  CAS  Google Scholar 

  100. Gavras H, Flessas A, Ryan TJ, Brunner HR, Faxon DP, Gavras I. Angiotensin II inhibition: treatment of congestive cardiac failure in a high-renin hypertension. JAMA 1977; 238: 880–882.

    Article  PubMed  CAS  Google Scholar 

  101. Wang Y-X, Gavras I, Wierzba T, Gavras H. Comparison of systemic and regional hemodynamic effects of a diuretic, an angiotensin-II receptor antagonist, and an angiotensin-converting enzyme inhibitor in conscious renovascular hypertensive rats. J Lab Clin Med 1992; 119: 267–272.

    PubMed  CAS  Google Scholar 

  102. Faxon DP, Creager MA, Halperin JL, Sussman HA, Gavras H, Ryan Ti. The effect of angiotensin converting enzyme inhibition on coronary blood flow and hemodynamics in patients without coronary artery disease. Int J Cardiol 1982; 2: 251–262.

    Article  PubMed  CAS  Google Scholar 

  103. Magrini F, Shimizu M, Roberts N, Fouad F, Tarazi RC, Zanchetti A. Converting enzyme inhibition and coronary blood flow. Circulation 1987; 75 (Suppl 1): 1168–1174.

    Google Scholar 

  104. Sladek CD. Regulation of vasopressin release by neurotransmitters, neuropeptides and osmotic stimuli. In: Gross BA, Leng C, eds. Neurophysics: Structure, Function and Control Progress in Brain Research. Elsevier, Amsterdam, 1983, pp. 71–90.

    Google Scholar 

  105. Ruocco NA Jr, Bergelson BA, Yu T-K, Gavras I, Gavras H. Augmentation of coronary blood flow by ACE inhibition: role of angiotensin and bradykinin. Clin Exper Hypertens 1995; 17: 1059–1072.

    Article  CAS  Google Scholar 

  106. Gavras H. Brunner HR, Laragh JH, Sealey JE, Gavras I, Vukovich RA. An angiotensin converting enzyme inhibitor to identify and treat vasoconstrictor and volume factors in hypertensive patients. N Engl J Med 1974; 291: 817–821.

    Article  PubMed  CAS  Google Scholar 

  107. Pfeffer MA, Pfeffer JA, Steinberg C, Finn P. Survival after an experimental myocardial infarction: beneficial effects of long-term therapy with captopril. Circulation 1985; 72: 406–412.

    Article  PubMed  CAS  Google Scholar 

  108. Sharpe N, Murphy J, Smith H, Hannan S. Treatment of patients with symptomless left ventricular dysfunction after myocardial infarction. Lancet 1988; 1: 255–259.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  110. Swedberg K, Held P, Kjekshus J, Rasmussen K, Ryden L, Wedel H. Effects of early administration of enalapril on mortality in patients with acute myocardial infarction (CONSENSUS II). N Engl J Med 1992; 327: 678–684.

    Article  PubMed  CAS  Google Scholar 

  111. Pfeffer MA, Braunwald E, Moye LA, Basta L, Brown EJ Jr, Cuddy TE. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the Survival and Ventricular Enlargement trial. The SAVE Investigators. N Engl J Med 1992; 327: 669–677.

    Article  PubMed  CAS  Google Scholar 

  112. The AIRE Study Investigators. Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. Lancet 1993; 342: 821–828.

    Google Scholar 

  113. Kober L, Torp-Pedersen C, Clarsen JE, Carlsen JE, Bagger H, Eliasen P. A clinical trial of the angiotensin-converting enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction. Trandolapril Cardiac Evaluation (TRACE) Study Group. N Engl J Med 1995; 333: 1670–1676.

    Google Scholar 

  114. Ambrosioni E, Borghi C, Magnani B. The Effect of the angiotensin-converting enzyme inhibitor zofenopril on mortality and morbidity after anterior myocardial infarction. SMILE Study Investigators. N Engl J Med 1995; 332: 80–85.

    Article  PubMed  CAS  Google Scholar 

  115. GISSI. GISSI-3: Effect of lisinopril and transermal glyceryl trinitrate singly and together on 6-week mortality and ventricular function after acute myocardial infarction. Lancet 1994; 343: 1115–1122.

    Google Scholar 

  116. Tigerstedt R, Bergman PG. Niere and Kreislauf. Skand Arch Physiol 1898; 8: 223–271.

    Article  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  118. Page IH, Helmer OM. A crystalline pressor substance (angiotonin) resulting from the reaction between renin and renin activator. J Exp Med 1940; 71: 29–42.

    Article  PubMed  CAS  Google Scholar 

  119. Braun-Menendez E, Fasciolo JC, Leloir LF, Munoz JM. The substance causing renal hypertension. J Physiol 1940; 98: 283–298.

    PubMed  CAS  Google Scholar 

  120. Laragh JH, Ames M, Kelly W, Lieberman S. Hypotensive agents and pressor substances. The effect of epinephrine, norepinephrine, angiotensin II, and others on the secretory rate of aldosterone in man. JAMA 1960; 174: 234–240.

    Article  PubMed  CAS  Google Scholar 

  121. TenEick RE, Houser SR, Bassett AL. Cardiac hypertrophy and altered cellular electrical activity of the myocardium: possible electrophysiological basis for myocardial contractility changes. In: Sperelakis N, ed. Physiology and Pathophysiology of the Heart, 2nd ed. Kluwer Academic, Boston, MA, 1989, pp. 57–94.

    Google Scholar 

  122. Katz AM. Cardiomyopathy of overload. A major determinant of prognosis in congestive heart failure. N Engl J Med 1990; 322: 100–110.

    Article  PubMed  CAS  Google Scholar 

  123. Manolis AJ, Beldekos D, Hatzissavas J, Foussas S, Cokkinos D, Bresnahan M, Gavras I, Gavras H. Hemodynamic and humoral correlates in essential hypertension. Relationship between patterns of LVH and myocardial ischemia. Hypertension 1997; 30 (Part 2): 730–734.

    Article  PubMed  CAS  Google Scholar 

  124. Kannel WB, Doyle JT, McNamara PM, Puickenton P, Gordon T. Precursors of sudden death; Factors related to the incidence of sudden death. Circulation 1975; 51: 606–613.

    Article  PubMed  CAS  Google Scholar 

  125. Nolly H, Carbini LA, Scicli G, Carrertero OA, Scicli AG. A local kallikrein-kinin system is present in rat hearts. Hypertension 1994; 23: 919–923.

    Article  PubMed  CAS  Google Scholar 

  126. Ling W. Shaper J, Wiemer G, Albus U, Scholkens BA. Ramipril prevents left ventricular hypertrophy with myocardial fibrosis without blood pressure reduction: a one year study in rats. Br J Pharmacol 1992; 107: 970–975.

    Article  Google Scholar 

  127. Rhaleb N-E, Yang X-P, Scicli AG, Carretero OA. Role of kinins and nitric oxide in the antihypertrophic effect of ramipril. Hypertension 1994; 23: 865–868.

    Article  PubMed  CAS  Google Scholar 

  128. Sadoshima J, Xu Y, Slayter HS, Izumo S. Autocrine release of angiotensin II mediates stretch-induced hypertrophy of cardiac myocytes in vitro. Cell 1993; 75: 977–984.

    Article  PubMed  CAS  Google Scholar 

  129. Pfeffer MA, Pfeffer JM. Reversing cardiac hypertrophy in hypertension. N Engl J Med 1990; 329: 1388–1390.

    Article  Google Scholar 

  130. Francis GS, Goldsmith SR, Levine TB, Olivari MT, Cohn JN. The neurohumoral axis in congestive heart failure. Am J Med 1984; 101: 370–377.

    CAS  Google Scholar 

  131. Gavras H, Faxon DP, Berkoben J, Brunner HR, Ryan TJ. Angiotensin converting enzyme inhibition in patients with congestive heart failure. Circulation 1978; 58: 770–775.

    Article  PubMed  CAS  Google Scholar 

  132. Turini GA, Brunner HR, Ferguson RK, Rivier JL, Gavras H. Congestive heart failure in normotensive man: hemodynamics, renin and angiotensin II blockade. Brit Heart J 1978; 40: 1134–1142.

    Article  PubMed  CAS  Google Scholar 

  133. The CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure: result of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). N Engl J Med 1987; 316: 1429–1435.

    Article  Google Scholar 

  134. The SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med 1991; 325: 293–302.

    Article  Google Scholar 

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

    Article  Google Scholar 

  136. Cohn JN, Johnson G, Ziesche S, Cobb F, Francis G, Tristawi F, et al. Comparison of enalapril with hydralazine-isosorbide dinitrate in the treament of chronic congestive heart failure. N Engl J Med 1991; 325: 303–310.

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. Haralambos Gavras
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  2. Irene Gavras
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Editors and Affiliations

  1. Department of Physiology, The University of Tennessee, Memphis, TN, USA

    Leonard Share PhD

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Gavras, H., Gavras, I. (1999). The Renin-Angiotensin System and the Heart. In: Share, L. (eds) Hormones and the Heart in Health and Disease. Contemporary Endocrinology, vol 21. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-708-6_4

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  • DOI: https://doi.org/10.1007/978-1-59259-708-6_4

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4757-5420-9

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