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Local Effects of Angiotensin-Converting Enzyme Inhibitors on the Vascular Wall

  • Chapter
Neurohumoral Regulation of Coronary Flow

Part of the book series: Developments in Cardiovascular Medicine ((DICM,volume 150))

  • 27 Accesses

Abstract

Angiotensin-converting-enzyme (ACE) inhibitors have gained a prominent role in the treatment of a variety of cardiovascular disorders. They have been shown not only effective in normalizing blood pressure in patients with hypertension 1,3 but also in the treatment of patients with congestive heart failure, in whom they exhibit beneficial hemodynamic effects and improve clinical symptoms and exercise tolerance4,5. More recently, it has been demonstrated that treatment with ACE-inhibitors not only reduces morbidity and mortality in CHF patients6,7, but also in cases following myocardial infarction8. The tremendous search for these and other new therapeutical applications of the ACE-inhibitors has lead to an improved understanding of the renin-angiotensin system. Although the renin- angiotensin system was initially regarded as a system present in the circulation, and dependent on the effects of renin and angiotensin production in plasma, it has become clear that “local” renin-angiotensin systems exist in target tissues that are important in cardiovascular regulation9,10. It is even possible that the major effects of ACE-inhibitors may not be through the blockade of the plasma angiotensin system, but rather, through effects on this local, tissue ACE systems11. Dzau et al. have hypothesized that the principal function of the circulating renin-angiotensin system is to provide short-term cardiovascular homeostasis, but that the tonic control of vascular resistance and local tissue function is influenced by the intrinsic tissue renin-angiotensin system12.

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References

  1. Atkinson AB, Brown JJ, Lever AF, Robertson JIS. Combined treatment of severe intractable hypertension with captopril and diuretic. Lancet 1980;2:105–8.

    Article  PubMed  CAS  Google Scholar 

  2. Gavras H, Brunner HR, Turini GA, et al. Antihypertensive effect of the oral angiotensin-converting enzyme inhibitor SQ 14225 in man. N Engl J Med 1978;298:991–5.

    Article  PubMed  CAS  Google Scholar 

  3. Laragh JH, Case DB, Atlas SA, Sealey JE. Captopril compared with other antirenin system agents in hypertensive patients: its triphasic effects on blood pressure and its use to identify and treat the renin factor. Hypertension 1980;2:586–93.

    Article  PubMed  CAS  Google Scholar 

  4. Giles TD, Katz R, Sullivan JM, et al. Short-and long-acting angiotensin-converting enzyme inhibitors: A randomized trial of lisinopril versus captopril in the treatment of congestive heart failure. J Am Coll Cardiol 1989;13:1240–7.

    Article  PubMed  CAS  Google Scholar 

  5. Kostis JB. Angiotensin converting enzyme inhibitors. II Clinical use. Am Heart J 1988;116: 1591–1605.

    Article  PubMed  CAS  Google Scholar 

  6. CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). N Engl J Med 1987;316:1429–35.

    Article  Google Scholar 

  7. 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 

  8. Pfeffer MA, Braunwald E, Moye LE, et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 1992;327:669–77.

    Article  PubMed  CAS  Google Scholar 

  9. Dzau VJ. Contributions of neuroendocrine and local autocrine-paracrine mechanisms to the pathofysiology and pharmacology of congestive heart failure. Am J Cardiol 1982; 62 (Suppl E): 76–81.

    Google Scholar 

  10. Unger Th, Gohlke P. Tissue renin-angiotensin systems in the heart and vasculature: possible involvement in the cardiovascular actions of converting enzyme inhibitors. Am J Cardiol 1990; 65 (Suppl l):3–10.

    Article  Google Scholar 

  11. Pitt B. Angiotensin-Converting Inhibitors in patients with congestive heart failure: A class effect ? Am J Cardiol 1991;68:106–8.

    Article  PubMed  CAS  Google Scholar 

  12. Dzau VJ. Circulating versus local renin-angiotensin system in cardiovascular homeostasis. Circulation 1988;77 (Suppl l):4–14.

    Google Scholar 

  13. Wilson SK, Lynch DR, Snyder SH. Angiotensin-converting enzyme labelled with 3H-Captopril. Tissue localization and changes in different models of hypertension in the rat. J Clin Invest 1987;80:841–51.

    Article  PubMed  CAS  Google Scholar 

  14. Jackson B, Cubela R, Johnston C. Angiotensin converting enzyme (ACE), characterization by I25-MK351A binding studies of plasma and tissue ACE during variation of salt status in the rat. J Hypertens 1986;4:759–65.

    Article  PubMed  CAS  Google Scholar 

  15. Velletri P, Bean BL. The effect of captopril on rat aortic angiotensin-converting enzyme. J Cardiovasc Pharmacol 1982;8:315–25.

    Article  Google Scholar 

  16. Loudon M, Bing RF, Thurston H, Swales JD. Arterial wall uptake of renal renin and blood pressure control. Hypertension 1983;5:629–34.

    Article  PubMed  CAS  Google Scholar 

  17. Molteni A, Dzau VJ, Fallon JT, Haber E. Monoclonal antibodies as probes of renin gene expression (abstr). Circulation 1984;70 (Suppl ll):196.

    Google Scholar 

  18. Dzau VJ. Possible prorenin activating mechanisms in the blood vessel wall. J Hypertension 1987;5 (Suppl 2):15–8.

    Google Scholar 

  19. Kifor I, Dzau VJ. Endothelial renin-angiotensin pathway: evidence for intracellular synthesis and secretion of of angiotensins. Circ Res 1987;60:422–8.

    Article  PubMed  CAS  Google Scholar 

  20. Lilly LS, Pratt RE, Alexander RW, et al. Renin expression by vascular endothelial cells in culture. Circ Res 1985;57:312.

    Article  PubMed  Google Scholar 

  21. Kawasaki H, Cline WH jr, Su C: Involvement of the vascular renin-angiotensin system in beta adrenergic receptor mediated facilitation of vascular neurotransmission in spontaneously hypertensive rats. J Pharmacol Exp Ther 1984;231:23–32.

    PubMed  CAS  Google Scholar 

  22. Gimbrone RW, Alexander RW: Angiotensin II stimulation of prostaglandin production in cultured human vascular endothelium. Science 1975;189:219–20.

    Article  PubMed  CAS  Google Scholar 

  23. Mizuno K, Nakamaru M, Highashimori K, Inagami T. Local generation and re-lease of angiotensin II in peripheral vascular tissue. Hypertension 1988;11:223–9.

    Article  PubMed  CAS  Google Scholar 

  24. Hirsch AT, Pinto YM, Schunkert H, Dzau VJ. Potential role of the tissue renin-angiotensin system in the pathofysiology of congestive heart failure. Am J Cardiol 1990;66 (Suppl D):22–32.

    Article  Google Scholar 

  25. Cushman DW, Wang FL, Fung WC, et al. Differentiation of angiotensin-converting enzyme (ACE) inhibitors by their selective inhibition of ACE in physiologically important target organs. Am J Hypertens 1989;2:294–306.

    PubMed  CAS  Google Scholar 

  26. Geisterfer AAT, Peach MJ, Owens GK. Angiotensin II induces hypertrophy not hyperplasia of cultured rat aortic smooth muscle cells. Circ Res 1988;62:749–56.

    Article  PubMed  CAS  Google Scholar 

  27. Campbell-Boswell M, Robertson AL: Effects of angiotensin II and vasopressin on human smooth cells in vitro. Exp Mol Pathol 1981;35:265–76.

    Article  PubMed  CAS  Google Scholar 

  28. Levy Bl, Michel JB, Salzman JL, Azizi, Poitevin, Safar M, Camilleri JP. Effects of chronic inhibition of converting enzyme on mechanical and structural properties of arteries in rat renovascular hypertension. Circ Res 1988;63:227–39.

    Article  PubMed  CAS  Google Scholar 

  29. Zwieten van PA, Jonge de A. Interaction between the adrenergic and renin-angiotensin-aldosterone systems. Postgrad Med J 1986;62:23–7.

    Article  PubMed  Google Scholar 

  30. Wenting GJ, Blankestijn PJ, Poldermans D, et al. Blood pressure response of nephrectomized subjects and patients with essential hypertension to ramipril: indirect evidence that inhibition of tissue angiotensin converting enzyme is important. Am J Cardiol 1987;59 (Suppl D):92–7.

    Article  Google Scholar 

  31. Cohen ML, Kurz KD. Angiotensin converting enzyme inhibition in tissues from spontaneously hypertensive rats after treatment with captopril or MK-421. J Pharmacol Exp Ther 1982;220:63–9.

    PubMed  CAS  Google Scholar 

  32. Cohen ML, Wiley KS, Kurz KD. Effect of acute oral administration of captopril and MK-421 on vascular angiotensin converting enzyme activity in the spontaneously hypertensive rat. Life Sci 1983;32:565–9.

    Article  PubMed  CAS  Google Scholar 

  33. Linger Th, Ganten D, Lang RE. Tissue converting enzyme and cardiovascular actions of converting enzyme inhibitors. J Cardiovasc Pharmacol 1986;8 (Suppl 10)75–81.

    Google Scholar 

  34. Levenson J, Chau NP, Billaud E, Simon A: Unrelated responses of brachial artery hemodynamics and renin angiotensin system to acute converting enzyme inhibition by enalaprilat in essential hypertension. Am J Cardiol 1988;61:1056–60.

    Article  PubMed  CAS  Google Scholar 

  35. Vanhoutte PM, Auch-Schwelk W, Biondi ML, Lorenz RR, Schini VB, Vidal MJ. Why are converting enzyme inhibitors vasodilators. Br J Clin Pharmac 1989;28:95–104.

    Article  Google Scholar 

  36. Kiowski W, Linder L, Kleinbloesem C, Brummelen van P, Buhler FR. Blood pressure control by the renin-angiotensin system in normotensive subjects; Assessment by angiotensin converting enzyme and renin inhibition. Circulation 1992;85:1–8.

    Article  PubMed  CAS  Google Scholar 

  37. Yanagisawa M, Kurihara H, Kimura S, et al. A novel potent vasoconstrictor peptide produced by vascualr endothelial cells. Nature 1988;332:411–5.

    Article  PubMed  CAS  Google Scholar 

  38. Weber KT, Anversa P, Armstrong PW, et al. Remoddeling and reparation in the cardiovascular system. J Am Coll Cardiol 1992;20:3–16.

    Article  PubMed  CAS  Google Scholar 

  39. Lerman A, Hildebrand F, Aarhus L, Burnett JC. Endothelin has biological actions at pathofysiological concentrations. Circulation 1991;83:1808–14.

    Article  PubMed  CAS  Google Scholar 

  40. Vallance P, Collier J, Moncada S: Effects of endothelium-derived nitric oxide on peripheral arteriolar tone in man. Lancet 1989;2:997–1000.

    Article  PubMed  CAS  Google Scholar 

  41. Yang HYT, Erdoss EG, Lewin Y. Characterization of a dipeptide hydrolase (kininase II: Angiotensin I converting enzyme). J Pharmacol Exp Ther 1971;177:291–300.

    PubMed  CAS  Google Scholar 

  42. Carbonell LF, Carretero OA, Stewart JM, Scicli AG: Effect of a kinin antagonist on the acute antihypertensive activity of enalaprilat in severe hypertension. Hypertension 1988;11:239–43.

    Article  PubMed  CAS  Google Scholar 

  43. Nishimura H, Kubo S, Ueyama M, Kubota J, Kawamura K. Peripheral hemodynamic effects of captopril in patients with congestive heart failure. Am Heart J 1989;117:100–5.

    Article  PubMed  CAS  Google Scholar 

  44. Wijngaarden van J, Tio RA, Gilst van WH, Graeff de PA, Langen de CDJ, Wesseling H. Basic pharmacology of ACE-inhibitors with respect to ischaemic heart disease: prostaglandins and bradykinin. Eur Heart J 1990;11 (Suppl B):84–93.

    PubMed  Google Scholar 

  45. Schror K. Converting enzyme inhibitors and the interaction between kinins and eicosanoids. J Cardiovasc Pharmacol 1990; 15 (Suppl 6):60–8.

    Google Scholar 

  46. Kaiser L, Spickard RC, Olivier NB. Heart failure depresses endothelium-dependent responses in canine femoral artery. Am J Physiol 1989;256:H962–H7.

    PubMed  CAS  Google Scholar 

  47. Dzau VJ, Packer M, Lilly LS, Swartz SL, Hollenberg NK, Williams GH. Prostaglandins in severe congestive heart failure. Relation to activation of the renin-angiotensin system and hyponatremia. N Engl J Med 1984;310:347–52.

    Article  PubMed  CAS  Google Scholar 

  48. Margulies K, Hildebrand F, Lerman A, Burnett JC Jr. Increased endothelin in experimental heart failure. Circulation 1990;82:2226–30.

    Article  PubMed  CAS  Google Scholar 

  49. Meulemans AL, Andries LJ, Brutsaert DL. Does endocardial endothelium mediate positive inotropic response to angiotensin I and angiotensin II. Circ Res 1990;66:1591–1601.

    Article  PubMed  CAS  Google Scholar 

  50. Gilst van WH, Scholtens E, Graeff de PA, Langen de CDJ, Wesseling H. Differential effects of angiotensin converting enzyme inhibitors on the coronary circulation. Circulation 1988;77(Suppl l):24–9.

    Google Scholar 

  51. Linz W, Scholkens BA, Han YF. Beneficial effects of the converting enzyme inhibitor, ramipril in ischemic rat hearts. J Cardiovasc Pharmacol 1986;8 (Suppl 10):91–9.

    Article  Google Scholar 

  52. Ertl G. Angiotensin converting enzym inhibition and ischaemic heart disease. Eur Heart J 1988;9:716–27.

    PubMed  CAS  Google Scholar 

  53. Pelc LR, Gross GJ, Warltier DC. Mechanism of coronary vasodilation produced by bradykinin. Circulation 1991;83:2048–56.

    Article  PubMed  CAS  Google Scholar 

  54. Baydoun AR, Woodward B. Effects of bradykinin in the rat isolated perfused rat heart: role of kinin receptors and endothelium-derived relaxing factor. Br J Pharmacol 1991:103:1829–33.

    Article  PubMed  CAS  Google Scholar 

  55. Gilst van WH, Graeff de PA, Leeuw de MJ, Scholtens E, Wesseling H. Converting enzyme inhibitors and the role of the sulfhydryl group in the potentiation of exo-and endogenous nitrovasodilators. J Cardiovasc Pharmacol 1991;18:429–36.

    Article  PubMed  Google Scholar 

  56. Tio RA, Wijngaarden van J, Scholtens E, Gilst van WH, Langen de CDJ, Wesseling H. The increase in coronary flow induced by converting enzyme inhibitors is prostacyclin independent. In: Schror K, ed. Prostaglandins in clinical research: cardiovascular system. New York: Alan R. Liss Inc 1989:435–9.

    Google Scholar 

  57. Friedman PL, Brown EJ, Gunther S, Alexander RW, Barry WH, Mudge GH, Grossman W. Coronary vasoconstrictor effect of indomethacin in patients with coronary artery disease. N Engl J Med 1981;305:1171–5.

    Article  PubMed  CAS  Google Scholar 

  58. Graeff de PA. Gilst van WH. Role of angiotensin-converting enzyme inhibition in angina pectoris. J Cardiovasc Pharmacol 1992;19 (Suppl 4):30–7.

    Article  Google Scholar 

  59. Tardieu A, Virot P, Vandroux H, Pinaud D, Chabanier A, Bensaid J. Effect of captopril on myocardial perfusion in patients with coronary insufficiency: Evaluation by the exercise test and quantitative myocardila tomoscintigraphy using thallium 201. Postgrad Med J 1986;62 (Suppl 1:38–41.

    PubMed  Google Scholar 

  60. Rietbrock N, Thurmann P, Kirsten R, Schneider W. Anti-ischaemic effect of enalapril in coronary heart disease; a randomised, placebo-controlled double blind trial. Dtsch Med Wschr 1988;113:300–2.

    Article  PubMed  CAS  Google Scholar 

  61. Bussman WD, Goerke S, Schneider W, Kaltenbach M. Angiotensin converting enzyme inhibitor in angina. Dtsch Med Wschr 1988;113:548–50.

    Article  Google Scholar 

  62. Klein WW, Khurmi NS, Eber B, Dusleag J. Effects of benazepril and metoprolol OROS alone and in combination on myocardial ischemia in patients with chronic stable angina. J Am Coll Cardiol 1990;16:948–56.

    Article  PubMed  CAS  Google Scholar 

  63. Ikram H, Low CJS, Shirlaw T, Webb CM, Richards AM, Crozier IG. Antianginal, hemodynamic and coronary vascular effects of captopril in stable angina pectoris. Am J Cardiol 1990;66:164–7.

    Article  PubMed  CAS  Google Scholar 

  64. Foult JM, Tavolaro O, Anthony I, Nitenberg A. Direct myocardial and coronary effects of enalaprilat in patients with dilated cardiomyopathy: Assessment by a bilateral intracoronary infusion technique. Circulation 1988;77:337–44.

    Article  PubMed  CAS  Google Scholar 

  65. Abrams J, Le Tourneau J. Angiotensin converting enzyme inhibition in the therapy of angina pectoris. Cardiovasc Drugs Ther 1987; 1:209.

    Article  Google Scholar 

  66. Cleland JF, Henderson E, McLenachan J, Findlay IN, Dargie HJ. Effect of captopril, an angiotensin-converting enzyme inhibitor, in patients with angina pectoris and heart failure. J Am Coll Cardiol 1991;17:733–9.

    Article  PubMed  CAS  Google Scholar 

  67. Braunwald E. ACE-inhibitors -a cornerstone of treatment of heart failure N Engl J Med 1991;325:351–3.

    Article  PubMed  CAS  Google Scholar 

  68. Powell JS, Clozell JP, Muller RKM, et al. Inhibitors of angiotensin-converting enzyme prevent myointimal proliferation after vascular injury. Science 1989;245:186–8.

    Article  PubMed  CAS  Google Scholar 

  69. The MERCATOR Study Group. Does the new angiotensin converting enzyme inhibitor cilazepril prevent restenosis after percutaneous transluminal coronary angioplasty? Results of the MERCATOR study: a multicenter, randomized, double-blind placebo-controlled trial. Circulation 1992;86:100–10.

    Article  Google Scholar 

  70. Grondin CM, Campeau L, Lesperance J, Enjalbert M, Bourassa MG. Comparison of late changes in internal mammary artery and saphenous vein graft in two consecutive series of patients 10 years after operation. Circulation 1984;70 (Suppl l):208–12.

    Google Scholar 

  71. Cameron A, Davies KB, Green GE, Meyers WO, Pettinger M. Clinical implications of the internal mammary artery bypass grafts: the Coronary Artery Surgery Study experience. Circulation 1988;77:815–9.

    Article  PubMed  CAS  Google Scholar 

  72. Luscher TF, Diederich D, Siebenmann R, et al. Difference between endothelium-dependent relaxation in arterial and in venous coronary bypass grafts. N Engl J Med 1988;319:462–7.

    Article  PubMed  CAS  Google Scholar 

  73. Chaikhouni A, Crawford FA, Kochel PJ, Olanoff LS, Halushka PV. Human internal mammary artery produces more prostacyclin than saphenous vein. J Thorac Cardiovasc Surg 1986;92:88–91.

    PubMed  CAS  Google Scholar 

  74. Oku T, Yamane S, Suma H, et al. Comparison of prostacyclin production of hu-man gastroepiploic artery and saphenous vein. Ann Thorac Surg 1990;49:767–70.

    Article  PubMed  CAS  Google Scholar 

  75. Buikema H, Grandjean JG, Broek van den SAJ, Gilst van WH, Wesseling H. Differences in vasomotor control between human gastroepiploic and left internal mammary artery. Circulation 1992;(Suppl)(in press).

    Google Scholar 

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  1. S. A. J. van den Broek MD
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  2. P. A. de Graeff MD
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  3. W. H. van Gilst M.D
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Editors and Affiliations

  1. Department of Clinical Pharmacology, University Hospital Groningen, Groningen, The Netherlands

    W. H. van Gilst

  2. Department of Cardiology Thorax-Center, University Hospital Groningen, Groningen, The Netherlands

    K. I. Lie

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van den Broek, S.A.J., de Graeff, P.A., van Gilst, W.H. (1993). Local Effects of Angiotensin-Converting Enzyme Inhibitors on the Vascular Wall. In: van Gilst, W.H., Lie, K.I. (eds) Neurohumoral Regulation of Coronary Flow. Developments in Cardiovascular Medicine, vol 150. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-1900-9_9

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  • DOI: https://doi.org/10.1007/978-94-011-1900-9_9

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