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AT1-Rezeptorblockade pp 1–10Cite as

Arterieller Hypertonus und das Renin-Angiotensin-System — genetische und transgene Studien

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Zusammenfassung

Die Bedeu tung des Renin-Angiotensin-Systems (RAS) als Mediator des arteriellen Blutdrucks und hochdruckinduzierter Endorganschäden wurde in den letzten Jahren intensiv untersucht. Ursprünglich wurde das RAS als endokrines System verstanden, das seine Wirkung über das Effektorpeptid Angiotensin II (ANG II) ausübt. Neuere Daten belegen die Existenz eines lokalen, gewebeständigen RAS, das durch parakrin-autokrine Mechanismen wirkt. Darüber hinaus wurden die Gene des RAS sequenziert und transgene Tiermodelle geschaffen, die unterschiedliche Komponenten des RAS überexprimieren. Als genetische Marker für den arteriellen Hypertonus und kardiovaskuläre Erkrankungen wurden verschiedene Genpolymorphismen untersucht. Sehr effektive Substanzen wurden entwickelt, die auf unterschiedlichen Ebenen des RAS angreifen.

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Literatur

  1. Barton M, Shaw S, d’Uscio LV, Moreau P, Luscher TF (1997) Angiotensin II increases vascular and renal endothelin-1 and functional endothelin converting enzyme activity in vivo: Role of ETA receptors for endothelin regulation. Biochem Biophys Res Comm 238: 861–865

    Article  CAS  PubMed  Google Scholar 

  2. Bohlender J, Fukamizu A, Lippoldt A, Nomura T, Dietz R, Menard J, Murakami K, Luft FC, Ganten D (1997) High human renin hypertension in transgenic rats. Hypertension 29: 428–34

    Article  CAS  PubMed  Google Scholar 

  3. Corvol P, Soubrier F, Jeunemaitre X (1997) Molecular genetics of the renin-angiotensin-aldosterone system in human hypertension. Pathol Biol Paris 45: 229–239

    CAS  PubMed  Google Scholar 

  4. Ganten U, Schroder G, Witt M, Zimmermann F, Ganten D, Stock G (1989) Sexual dimorphism of blood pressure in spontaneously hypertensive rats: Effects of anti-androgen treatment. J Hypertens 7: 721–726

    Article  CAS  PubMed  Google Scholar 

  5. Grady EE, Sechi LA, Griffin CA, Schambelan M, Kalinyak JE (1991) Expression of AT2 receptors in the developing rat fetus. J Clin Invest 88: 921–933

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Hein L, Barsh GS, Pratt RE, Dzau VJ, Kobilka BK (1995) Behavioural and cardiovascular effects of disrupting the angiotensin II iype-2 receptor in mice. Nature 377: 744–747

    Article  CAS  PubMed  Google Scholar 

  7. Ichiki T, Labosky PA, Shiota C, Okuyama S, Imagawa Y, Fogo A, Niimura F, Ichikawa I, Hogan BL, Inagami T (1995) Effects on blood pressure and exploratory behaviour of mice lacking angiotensin II type-2 receptor. Nature 377: 748–750

    Article  CAS  PubMed  Google Scholar 

  8. Jeunemaitre X, Soubrier F, Kotelevtsev YV, Lifton RP, Williams CS, Charru A, Hunt SC, Hopkins PN, Williams RR, Lalouel JM, et al. (1992) Molecular basis of human hypertension: Role of angiotensinogen. Cell 71: 169–180

    Article  CAS  PubMed  Google Scholar 

  9. Kimura S, Mullins JJ, Bunnemann B, Metzger R, Hilgenfeldt U, Zimmermann F, Jacob H, Fuxe K, Ganten D, Kaling M (1992) High blood pressure in transgenic mice carrying the rat angiotensinogen gene. EMBO J 11:821–827

    CAS  PubMed Central  PubMed  Google Scholar 

  10. Krege JH, John SW, Langenbach LL, Hodgin JB, Hagaman JR, Bachman ES, Jennette JC, O’Brien DA. Smithies O (1995) Male-female differences in fertility and blood pressure in ACE-deficient mice. Nature 375: 146–148

    Article  CAS  PubMed  Google Scholar 

  11. Krege JH, Kim HS, Moyer JS, Jennette JC, Peng L, Hiller SK, Smithies O (1997) Angiotensin-Converting enzyme gene mutations, blood pressures, and cardiovascular homeostasis. Hypertension 29: 150–157

    Article  CAS  PubMed  Google Scholar 

  12. Lee MA, Böhm M, Paul M, Bader M, Ganten U, Ganten D (1996) Physiological characterization of the hypertensive transgenic rat TGR(mREN2)27. Am J Physiol 270: E919–929

    CAS  PubMed  Google Scholar 

  13. Lindpaintner K, Lee M, Larson MG, Rao VS, Pfeffer MA, Ordovas JM, Schaefer EJ, Wilson AF, Wilson PW, Vasan RS, Myers RH, Levy D (1996) Absence of association or genetic linkage between the angiotensin- converting-enzyme gene and left ventricular mass. N Engl J Med 334: 1023–1028

    Article  CAS  PubMed  Google Scholar 

  14. Lindpaintner K, Pfeffer MA, Kreutz R, Stampfer MJ, Grodstein F, LaMotte F, Buring J, Hennekens CH (1995) A prospective evaluation of an angiotensin-converting-enzyme gene polymorphism and the risk of ischemic heart disease. N Engl J Med 332: 706–711

    Article  CAS  PubMed  Google Scholar 

  15. Lo M, Liu KL, Lantelme P, Sassard J (1995) Subtype 2 of angiotensin II receptors controls pressure- natriuresis in rats. J Clin Invest 95: 1394–1397

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. McDonald KM, Garr M, Cariyle PF, Francis GS, Hauer K, Hunter DW, Parish T, Stillman A, Cohn JN (1994) Relative effects of alpha 1-adrenoceptor blockade, converting enzyme inhibitor therapy, and angiotensin II subtype 1 receptor blockade on ventricular remodeling in the dog. Circulation 90: 3034–3046

    Article  CAS  PubMed  Google Scholar 

  17. Merrill DC, Thompson MW, Carney CL, Granwehr BP, Schlager G, Robillard JE, Sigmund CD (1996) Chronic hypertension and altered baroreflex responses in transgenic mice containing the human renin and human angiotensinogen genes. J Clin Invest 97: 1047–1055

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Morgan K (1994) Diverse factors influencing angiotensin metabolism during ACE inhibition: Insights from molecular biology and genetic studies. Br Heart J 72 (Suppl): S3–10

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Mullins JJ, Peters J, Ganten D (1990) Fulminant hypertension in transgenic rats harbouring the mouse Ren-2 gene. Nature 344: 541–544

    Article  CAS  PubMed  Google Scholar 

  20. MuUins JJ, Sigmund CD, Kane Haas-C, Wu CZ, Pacholec F, Zeng Q, Gross KW (1988) Studies on the regulation of renin genes using transgenic mice. Clin Exp Hypertens A 10: 1157–1167

    Google Scholar 

  21. Nickenig G, Laufs U, Schnabel P, Knorr A, Paul M, Böhm MP (1997) Down-regulation of aortic and cardiac ATI receptor gene expression in transgenic (mRen-2) 27 rats. Br J Pharmacol 121: 134–140

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Paul M, Wagner J, Kreutz R, Fernandez Alfonso MS, Liu Y, Bader M, Ganten D (1994) Transgenic Rats Expressing Components of the Renin-Angiotensin System: Focus on Cardiovascular Regulation. In Lindpainter K, Ganten D (eds) New York: The Cardiac-Renin Angiotensin System. Futura Publishing Co., Inc., Armonk, pp 289–307

    Google Scholar 

  23. Peters J (1995) Molecular basis of human hypertension: The role of angiotensin. Baillieres Clin Endocrinol Metab 9: 657–678

    Article  CAS  PubMed  Google Scholar 

  24. Pieruzzi F, 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  CAS  PubMed  Google Scholar 

  25. Pinto YM, Buikema H, van Gilst WH, Scholtens E, van Geel PP, de Graeff PA, Wagner J, Paul M (1997) Cardiovascular end-organ damage in Ren-2 transgenic rats compared to spontaneously hypertensive rats. J Mol Med 75:371–377

    Article  CAS  PubMed  Google Scholar 

  26. Schmidt S, Ritz E (1997) Genetics of the renin-angiotensin system and renal disease: A progress report. Curr Opin Nephrol Hypertens 6: 146–151

    Article  CAS  PubMed  Google Scholar 

  27. Schmidt S, Schone N, Ritz E (1995) Association of ACE gene polymorphism and diabetic nephropathy? Kidney Int 47: 1176–1181

    Article  CAS  PubMed  Google Scholar 

  28. Smits JF, Daemen MJ (1994) Insights from animal models of myocardial infarction: Do ACE inhibitors limit the structural response? Br Heart J 72 (Suppl): S61–64

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Tiret L, Bonnardeaux A, Poirier O, Ricard S, Marques-Vidal P, Evans A, Arveiler D, Luc G, Kee F, Ducimetiere P et al. (1994) Synergistic effects of angiotensin-converting enzyme and angiotensin-II type 1 receptor gene polymorphisms on risk of myocardial infarction. Lancet 344: 910–913

    Article  CAS  PubMed  Google Scholar 

  31. Ward K, Hata A, Jeunemaitre X, Helin C, Nelson L, Namikawa C, Farrington PF, Ogasawara M, Suzumori K, Tomoda S et al. (1993) A molecular variant of angiotensinogen associated with preeclampsia. Nat Genet 4:59–61

    Article  CAS  PubMed  Google Scholar 

  32. Zisman LS, Abraham WT, Meixell GE, Vamvakias BN, Quaife RA, Lowes BD, Roden RL, Peacock SJ, Groves BM, Raynolds MV et al. (1995) Angiotensin II formation in the intact human heart. Predominance of the angiotensin-converting enzyme pathway. J Clin Invest 96: 1490–1498

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Authors and Affiliations

  1. Institut für klinische Pharmalogie und Toxikologie, Freie Universität Berlin, Deutschland

    L. Rothermund & Prof. Dr. Martin Paul

  2. Institut für klinische Pharmakologie und Toxikologie, Freie Universität Berlin, Garystraße 5, D-14195, Berlin, Deutschland

    Prof. Dr. Martin Paul

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  1. L. Rothermund
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  2. Prof. Dr. Martin Paul
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Editors and Affiliations

  1. Institut für experimentelle und klinische Pharmakologie und Toxikologie, Medizinische Universität zu Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Deutschland

    Peter Dominiak

  2. Abteilung für Pathophysiologie, Zentrum für Innere Medizin, Universitätsklinikum Essen, Hufelandstrasse 55, 45122, Essen, Deutschland

    Gerd Heusch

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© 1999 Dr. Dietrich Steinkopff Verlag GmbH & Co. KG, Darmstadt

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Rothermund, L., Paul, M. (1999). Arterieller Hypertonus und das Renin-Angiotensin-System — genetische und transgene Studien. In: Dominiak, P., Heusch, G. (eds) AT1-Rezeptorblockade. Steinkopff, Heidelberg. https://doi.org/10.1007/978-3-642-93701-9_1

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  • DOI: https://doi.org/10.1007/978-3-642-93701-9_1

  • Publisher Name: Steinkopff, Heidelberg

  • Print ISBN: 978-3-642-93702-6

  • Online ISBN: 978-3-642-93701-9

  • eBook Packages: Springer Book Archive

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