Zusammenfassung
Während das zirkulierende Renin-Angiotensin-System (RAS) bei der kurzfristigen Aufrechterhaltung der kardiovaskulären Homöostase eine wichtige Rolle spielt, weisen neueste Studien darauf hin, daß das endogene RAS in Zielgeweben eine Rolle bei der langfristigen kardiovaskulären Regulation spielt. Dieser Artikel konzentriert sich auf die verschiedenen Wirkungen des Angiotensin Converting Enzyme (ACE) im Gewebe und von Angiotensin II (Ang II), seinem aktiven Peptidprodukt. Von Angiotensin II wurde nachgewiesen, daß es in glatten Gefäßmuskelzellen ein potenter Wachstumsfaktor ist. Je nach den lokalen Gegebenheiten kann die vaskuläre Reaktion eine Hypertrophie oder eine Hyperplasie sein. Die molekularen Mechanismen, die bei den Interaktionen von Angiotensin II mit Zellprodukten aus Endothel- oder glatten Muskelzellen beteiligt sind, können bei der Modulation der Gefäßstruktur bei der Hypertonie und bei einer Gefäßschädigung eine wichtige Rolle spielen. Auch gibt es Hinweise dafür, daß Angiotensin II bei der Entwicklung einer linksventrikulären Hypertrophie beim Hochdruck eine Rolle spielt. Darüber hinaus kann das kardiale RAS zur Pathophysiologie der Herzinsuffizienz beitragen. Experimentelle und klinische Studien mit ACE-Hemmern deuten darauf hin, daß die ACE-Aktivität im Gewebe bei der Entwicklung der Atherosklerose, bei der kardialen Hypertrophie und beim kardialen Umbau von Bedeutung ist.
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Literatur
Aberg G, Ferrer P(1990) Effects of captopril on atherosclerosis in cynomolgus monkeys. J Cardiovasc Pharmacol 15 (suppl 5 ): 65–72
Admiraal PJJ, Derkx FHM, Jan Danser AH, Pieterman H, Schalenkamp MADH (1990) Metabolism and production of angiotensin I in different vascular beds in subjects with hypertension.. Hypertension 15: 44–55
Alhenc-Gelas F, Soubrier F, Hubert C, Allegrini J, Corvol P (1989) The peculiar characteristics of the amino acid sequence of angiotensin I-converting enzyme, as determined by cDNA cloning of the human endothelial enzyme. J Cardiovasc Pharmacol 14 (suppl 4): 6–9
Alhenc-Gelas F, Soubrier F, Hubert C, Allegrini J, Lattion AL, Corvol P (1990) The angiotensin I-converting enzyme (kininase II): progress in molecular and genetic structure. J Cardiovasc Pharmacol 15 (suppl 6): 25–29
Becker RHA, Weimer G, Linz W (1991) Preservation of endothelial function by ramipril in rabbits on a long-term atherogenic diet. J Cardiovasc Pharmacol 18 (suppl 2): S110 — S115
Cambien F, Poirier O, Lecerf L, Evans A, Cambou JP, Arveller D, Luc G, Bard JM, 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
Campbell DJ (1985) The site of angiotensin production. J Hypertension 3: 730–737
Campbell DJ (1987) Circulating and tissue angiotensin systems. J Clin Invest 79: 1–6
Carretero OA, Miyazaki S, Scicli AG (1981) Role of kinins in the acute antihypertensive effect of the converting enzyme inhibitor, captopril. Hypertension 3: 18–22
Chevillard C, Brown NL, Jouquey S, Mathiou M-N, Laliberte F, Gamon G (1989) Cardiovascular actions and tissue-converting enzyme inhibitory effects of chronic enalapril and trandolapril treatment of spontaneously hypertensive rats. J Cardiovasc Pharmacol 14: 297–301
Chobanian AV (1990) The effects of ACE inhibitors and other antihypertensive drugs on cardiovascular risk factors and atherogenesis. Clin Cardiol 13:VII-43—VII-48
Chobanian AV, Haudenschild CC, Nickerson C, Drago R (1990) Antiatherogenic effect of captopril in the Watanabe heritable hyperlipidemic rabbit. Hypertension 15: 327–331
Crawford DC, Chobanian AV, Brecher P (1992) Angiotensin II increases fibronectin expression in rat cardiac fibroblasts in vivo (Abstr). Circulation 86 (suppl I): I - 89
Daemen MJAP, Lombardi DM, Bosman FT, Schwartz SM (1991) Angiotensin II induces smooth muscle cell proliferation in the normal and injured rat arterial wall. Circ Res 68: 450–456
Dahlöf B, Pennert K, Hansson L (1992) Reversal of left ventricular hypertrophy in hypertensive patients. A metaanalysis of 109 treatment studies. Am J Hypertension 5: 95–110
Drexler H, Lindpaintner K, Lu W, Schieffer B, Ganten D (1989) Transient increase in the expression of cardiac angiotensinogen in a rat model of myocardial infarction and failure (Abstr). Circulation 80 (suppl II): II - 459
Dzau V (1987) Vascular angiotensin pathways: new therapeutic target. J Cardiovasc Pharmacol 10 (suppl 7): 9–16
Dzau VJ, Colucci WS, Hollenberg NK, Williams GH (1981) Relation of the renin-angiotensin-aldosterone system to clinical state in congestive heart failure. Circulation 63: 645–651
Dzau VJ, Ellison KE, Brody T, Ingelfinger J, Pratt RE (1987) A comparative study of the distributions of renin and angiotensinogen messenger ribonucleic acids in rat and mouse tissues. Endocrinology 120: 2334–2338
Dzau VJ, Gibbons GH (1987) Autocrine-paracrine mechanisms of vascular myocytes in hypertension. Am J Cardiol 60: 991–1031
Dzau VJ, Gibbons GH, Pratt RE (1991) Molecular mechanisms of vascular renin-angiotensin system in myointimal hyperplasia. Hypertension 18 (suppl 1I):II-100—II-105
Dzau VJ, Pratt RE (1986) Renin-angiotensin system: biology, physiology and pharmacology. In: Haber E, Morgan H, Katz A, Fozzard H (eds) Handbook of experimental cardiology; Raven Press, New York, pp 1631–1661
Dzau VJ, Re RN (1987) Evidence for the existence of renin in the heart. Circulation 73 (suppl I): 1134–1136
Eichstaedt H, Danne O, Langer M, Cordes M, Schubert C, Felix R, Schmutzler H (1989) Regression of left ventricular hypertrophy under ramipril treatment investigated by nuclear magnetic resonance imaging. J Cardiovasc Pharmacol 13 (suppl 3): 75–80
Fabris B, Jackson B, Kohzuki M, Perich R, Johnston CI (1990) Increased cardiac angiotensin-converting enzyme in rats with chronic heart failure. Clin Exp Pharmacol Physiol 17: 309–314
Farhy RD, Ho KL, Carretero OA, Scicli AG (1992) Kinins mediate the antiproliferative effect of ramipril in rat carotid artery. Biochem and Biophys Res Comm 182: 283–288
Folkow B (1990) “Structural factor” in primary and secondary hypertension. Hypertension 16:89–101
Ganten D, Hutchinson JS, Haebara H, Schelling P, Fischer H, Ganten U (1976) Tissue iso-renins. Clin Sci Mol Med 51: 117–120
Garavaglia GE, Messerli FH, Nunez BD, Schmieder RE, Frohlich ED (1988) Immediate and short-term cardiovascular effects of a new converting enzyme inhibitor (lisinopril) in essential hypertension. Am J Cardiol 62: 912–916
Geisterfer AAT, Peach MJ, Owens GK (1988) Angiotensin II induces hypertrophy, not hyperplasia, of cultured rat aortic smooth muscle cells. Circ Res 62: 749–756
Gibbons GH, Pratt RE, Dzau VJ (1989) Angiotensin is a bifunctional modulator of vascular smooth muscle cell growth: Interaction with basic fibroblast growth factor (abstract). Hypertension 14: 358
Gibbons GH, Pratt RE, Dzau VJ (1992) Vascular smooth muscle cell hypertrophy vs. hyperplasia: autocrine transforming growth factor-131 expression determines growth response to angiotensin II. J Clin Invest 90: 456–461
Gibbons GH, Pratt RE, Dzau VJ (1992) Role of autocrine transforming growth factor-ß1 expression and activation in determining vascular myocyte growth response to angiotensin II versus basic fibroblast growth factor ( Abstr ). Clin Res 39: 287A
Griendling KK, Berk BC, Ganz P, Gimbrone MA, Alexander RW (1987) Angiotensin II stimulation of vascular smooth muscle phosphoinositide metabolism: state of the art lecture. Hypertension 9 (suppl 3):III-181—III-185
Hermans WR, Rensing BJ, Foley DP, Deckers JW, Rutsch W, Enamuelsson H, Danchin N, Wijns W, Chappuis F, Serruys PW (1992) Therapeutic dissection after successful coronary balloon angioplasty: No influence on restenosis or on clinical outcome in 693 patients. J Am Coll Cardiol 20: 767–780
Hilgers KF, Kuczera M, Wilhem MJ, Wiecek A, Ritz E, Ganten D, Mann JFE (1989) Angiotensin formation in the isolated rat hindlimb. J Hypertension 7: 789–798
Hirsch AT, Dzau VJ (1990) Tissue renin-angiotensin systems in the pathophysiology of heart failure. In: Brachmann J, Dietz R, Kübler W (eds) Heart failure and arrhythmias; Springer-Verlag, Heidelberg
Hirsch AT, Talsness CE, Schunkert H, Paul M, Dzau VJ (1991) Tissue-specific activation of cardiac angiotensin-converting enzyme in experimental heart failure. Circ Res 69: 475–482
Hirsch AT, Talsness CE, Smith AD, Schunkert H, Ingelfinger JR, Dzau VJ (1992) Differential effects of captopril and enalapril on tissue renin-angiotensin systems in experimental heart failure. Circulation 86: 1566–1574
Ichikawa I, Brenner BM (1984) Glomerular actions of angiotensin II. Am J Med 76: 43–49
Itoh H, Pratt RE, Dzau VJ (1990) Atrial natriuretic factor inhibits hypertrophy of vascular smooth muscle cells. J Clin Invest 86: 1690–1697
Jackson B, Mendelsohn FA, Johnston CI (1991) Angiotensin-converting enzyme inhibition: prospects for the future. J Cardiovasc Pharmacol 18 (suppl 7): 4–8
Jayakody L, Kappagoda T, Senaratne MPJ, Thomson ABR (1988) Impairment of endothelium-dependent relaxation: an early marker for atherosclerosis in the rabbit. Br J Pharmacol 94: 335–346
Katoh Y, Komuro I, Shibasaki Y, Yamaguchi H, Yazaki Y (1989) Angiotensin II induces hypertrophy and oncogene expression in cultured rat heart myocytes (Abstr). Circulation 80 (suppl II): II - 450
Koch Weser J (1964) Myocardial actions of angiotensin II. Circ Res 14: 337–344
Koch-Weser J (1965) Nature of the inotropic action of angiotensin on ventricular myocardium. Circ Res 16: 230–237
Komuro I, Kurabayashi M, Takaku F, Yazaki Y (1988) Expression of cellular oncogenes in the myocardium during the developmental state and pressure-overloaded hypertrophy of the rat heart. Circ Res 62: 1075–1079
Kubo SH, Clark M, Laragh JH, Borer JH, Cody RI (1987) Identification of normal neurohormonal activity in mild congestive heart failure and stimulating effect of upright posture and diuretics. Am J Cardiol 60: 1322–1328
Lindpaintner K, Jin M, Wilhelm MJ, Suzuki F, Linz W, Schoelkens BA, Ganten D (1988) Intracardiac generation of angiotensin and its physiologic role. Circulation 77 (suppl 1): 1–18
Linz W, Scholkens BA, Ganten D (1989) Converting enzyme inhibition specifically prevents the development and induces regression of cardiac hypertrophy in rats. Clin Ex-per Hypertens All(7): 1325–1350
Michel JB, Cattion AL, Salzmann JL, de Lourdes Cerol M, Phillipe M, Camilleri JP, Coruol P (1988) Hormonal and cardiac effects of converting enzyme inhibition in rat myocardial infarction. Circ Res 62: 641–650
Muller J, Lund EG, Hofstetter L, Brunner DB, Haldy P (1982) Stimulation of aldosterone biosynthesis by sodium sequestration: role of angiotensin II. Am J Physiol 243: E450 — E457
Naftilan AJ, Pratt RE, Dzau VJ (1989) Induction of platelet-derived growth factor A-chain and c-myc gene expressions by angiotensin II in cultured rat vascular smooth muscle cells. J Clin Invest 83: 1419–1424
Naftilan AJ, Pratt RE, Eldridge CS, Lin HL, Dzau VJ (1989) Angiotensin II c-fos expression in smooth muscle via transcriptional control. Hypertension 13: 706–711
Nakashima Y, Fouad FM, Tarazi RC (1984) Regression of left ventricular hypertrophy from systemic hypertension by enalapril. Am J Cardiol 53: 1044–1049
Okamura T, Myazcki M, Inagemi T, Toda N (1986) Vascular renin-angiotensin system in two-kidney, one-clip hypertensive rats. Hypertension 8: 560–565
Oliver JA, Sciacca RR (1984) Local generation of angiotensin II as a mechanism of regulation of peripheral vascular tone in the rat. J Clin Invest 74: 1247–1251
Oren S, Messerli FH, Grossman E, Garavaglia GE, Frolich ED (1991) Immediate and short-term effects of fosinopril, a new angiotensin converting enzyme inhibitor, in patients with essential hypertension. J Am Coll Cardiol 17: 1183–1187
Paul M, Schunkert H, Allen P, Dzau VJ (1990) Widespread distribution of angiotensin converting enzyme mRNA in human tissues. J Hypertens 8 (suppl 3): 36
Pfeffer JM, Pfeffer MA (1988) Angiotensin converting enzyme inhibition and ventricular remodeling in heart failure. Am J Med 84: 37–44
Pfeffer JM, Pfeffer MA, Fletcher PJ, Braunwald E (1991) Progressive ventricular remodeling in rat with myocardial infarction. Am J Physiol 260 (Pt. 2): H1406–1414
Pfeffer et al., The SAVE Investigators (1992) Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 327: 669–677
Powell JS, Clozel JP, Muller RKM, Kuhn H, Hefti F, Hosang M, Baumgartner HR (1989) Inhibitors of angiotensin-converting enzyme prevent myointimal proliferation after vascular injury. Science 245: 186–188
Rakugi H, Jacob HJ, Ingelfmger JR, Krieger JE, Dzau VJ, Pratt RE (1990) Angiotensinogen gene expression in the myointima after vascular injury (abstract). Hypertension 16: 345
Rakugi H, Krieger J, Wang DS, Dzau VJ, Pratt RE (1991) Induction of angiotensin converting enzyme in neointima after balloon injury. Circulation 84 (suppl II): II - 113
Ragazzi E, Froldi G, Pandolfo L et al. (1989) Segmental impairment of endothelium-mediated relaxation in thoracic aortas from atherosclerotic rabbits. Comparison to cholesterol infiltration and energy metabolism. Artery 16: 327–345
Reidy MA, Fingerle J, Au YP, Majesky MW (1989) Correlation of mRNA expression of cellular mitogens and smooth muscle cell proliferation in arteries denuded of endothelium (Abstr). J Cell Biochem 13E (suppl 13): 194
Rosenthal JH, Pfieffer B, Mecheilor ML, Pschorr J, Jacob ICM, Dahlheim H (1984) Investigations of components of the renin-angiotensin system in rat vascular tissue. Hypertension 6: 383–390
Sakaguchi K, Chai SY, Jackson B, Johnston CI, Mendelsohn FA (1988) Inhibition of tissue angiotensin converting enzyme. Quantitation by autoradiography. Hypertension 11: 230–238
Schunkert H, Dzau VJ, Tang SS, Hirsch AT, Apstein CS, Lorell BH (1990) 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 86: 1913–1920
Skidgel RA, Defendini R, Erdos EG (1988) Angiotensin I converting enzyme and its role in neuropeptide metabolism. In: Turner AJ (ed) Neuropeptides and their peptidases; Ellis Horwood VCH, pp 165–188
The SOLVD Investigators (1992) Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. N Engl J Med 327: 685–691
Taubman MB, Berk BC, Izumo S, Tsuda T, Alexander RW, Nadal-Ginard B (1989) Angiotensin II induces c-fos mRNA in aortic smooth muscle. Role of Ca++ mobilization and protein kinase C activation. J Biol Chem 264: 526–530
Urata H, Healey B, Stewart RW, Bumpus FM, Husain A (1989) Angiotensin II receptors in normal and failing human hearts. J Clin Endocrinol Metab 69: 54–66
Urata H, Healey B, Stewart RW, Bumpus FM, Husain A (1990) Angiotensin II-forming pathways in normal and failing human hearts. Circ Res 66: 883–890
Vlodaysky I, Folkman J, Sullivan R, Fridman R, Ishai-Michaeli R, Sasse J, Klagsbrun M (1987) Endothelial cell-derived basic fibroblast growth factor: Synthesis and deposition into subendothelial extracellular matrix. Proc Natl Acad Sci USA 84: 2292–2296
Webb RC, Finta KM, Fisher M, Lee L, Pitt B (1992) Ramipril reverses impaired endothelium-dependent relaxation in arteries from rabbits fed an atherogenic diet. The FASEB Journal 6(No. 5: Part I ): Abstract 3022
Weber KT, Brilla CG, Janicki JS, Reddy HK (1991) Myocardial fibrosis: role of ventricular systolic pressure, arterial hypertension, and circulation hormones. Basic Res Cardiol 86 (suppl 3): 25–31
Yamada H, Fabris B, Allen AM, Jackson B, Johnson CI, Mendelsohn FAO (1991) Localisation of angiotensin converting enzyme in the rat heart. Circ Res 68: 141–149
Xiang J, Linz W, Becker H, Ganten D, Lang RE, Schoelkens B, Unger T (1984) Effects of converting enzyme inhibitors: ramipril and enalapril on peptide action and sympathetic neurotransmission in the isolated rat heart. Eur J Pharmacol 113: 215–223
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Dzau, V.J. (1993). Lokale Expression und pathophysiologische Rolle von Renin-Angiotensin im Gefäßsystem und im Herzen. In: Grobecker, H., Heusch, G., Strauer, B.E. (eds) Angiotensin und Herz. Steinkopff, Heidelberg. https://doi.org/10.1007/978-3-662-11145-1_1
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DOI: https://doi.org/10.1007/978-3-662-11145-1_1
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