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Angiotensin Receptor Antagonists and Cardiovascular Remodeling

  • K. Sabri
  • C. Chassagne
  • B. Lévy
  • J.L. Samuel
  • L. Rappaport
Part of the Progress in Experimental Cardiology book series (PREC, volume 2)

Summary

Angiotensin (Ang) II is one of the key hormones involved in cardiovascular homeostasis. It has potent vasoconstrictor effects and is directly involved in the vascular and cardiac remodeling observed in response to chronic or acute hypertension. Two major Ang II receptor subtypes, AT1 and AT2, have been described, and their roles in vivo and in vitro have now been investigated using nonpeptidic antagonists, losartan and PD123319, which block AT1 and AT2 receptors respectively. The aim of this review is to focus on in vivo data to better define the respective functions of the AT1 and AT2 receptor subtypes. In adult rats, the AT1 receptor subtype does not trigger trophic effects directly in cardiomyocytes, whereas the AT2 receptor may have a major trophic role in smooth muscle cells.

Keywords

Cardiac Hypertrophy Medial Hypertrophy Cardiovascular Remodel Smooth Muscle Cell Phenotype Angiotensin Blockade 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Griendling KK, Alexander RW. 1995. Angiotensin, other pressors and the transduction of vascular smooth muscle contraction. In Hypertension, pathophysiology, diagnosis and management, Ed. Brenner Larragh, 524–541. New York: Raven Press.Google Scholar
  2. 2.
    Crawford DC, Chobanian AV, Brecher P. 1994. Angiotensin II induces fibronectin expression associated with cardiac fibrosis in the rat. Circ Res 74:727–739.PubMedCrossRefGoogle Scholar
  3. 3.
    Chassagne C, Servant M, Meloche S. 1996. Rôles et voies de signalisation des récepteurs de l’angiotensine II dans la croissance cellulaire. Medecine et Sciences 12:1351–1360.CrossRefGoogle Scholar
  4. 4.
    de Gasparo M, Husain A, Alexander W, Catt KJ, Chiu AT, Drew M, Goodfriend T, Harding JW, Inagami T, Timmermans PBMWM. 1995. Proposed update of angiotensin receptor nomenclature. Hypertension 25:924–927.PubMedCrossRefGoogle Scholar
  5. 5.
    Timmermans PBMWM, Wong PC, Chiu AT, Herblin WF, Benfield P, Carini DJ, Lee RJ, Wexler RR, Saye JAM, Smith RD. 1993. Angiotensin II receptors and angiotensin II receptor antagonists. Pharmacol Rev 45:205–251.PubMedGoogle Scholar
  6. 6.
    Brink M, de Gasparo M, Rogg H, Whitebread S, Bullock G. 1995. Localization of angiotensin II receptor subtypes in the rabbit heart. J Mol Cell Cardiol 27:459–470.PubMedCrossRefGoogle Scholar
  7. 7.
    Lopez JJ, Lorell BH, Ingelfinger JR, Weinberg EO, Schunkert H, Diamant D, Tang SS. 1994. Distribution and function of cardiac angiotensin AT1-and AT2-receptor subtypes in hypertrophied rat hearts. Am J Physiol 36:H844–H852.Google Scholar
  8. 8.
    Wolf K, Delia Bruna R, Bruckschlegel G, Schunkert H, Riegger GA, Kurtz A. 1996. Angiotensin II receptor gene expression in hypertrophied left ventricles of rat hearts. J Hypertens 14(3):349–354.PubMedCrossRefGoogle Scholar
  9. 9.
    Zhuo J, Allen AM, Alcorn D, Aldred GP, MacGregor DP, Mendelsohn FAO. 1995. The distribution of angiotensin II receptors. In Hypertension: Pathophysiology, diagnosis and management. Ed. JH Laragh and BM Brenner, 1739–1762. New York: Raven Press.Google Scholar
  10. 10.
    Lassègue B, Griendling KK, Alexandre W. 1994. Molecular biology of angiotensin II receptors. Ed. JM Saavedra and PBMWM Timmermans, 17–48. New York: Plenum Press.CrossRefGoogle Scholar
  11. 11.
    Meggs LG, Coupet J, Huang H, Cheng W, Li P, Capasso JM, Homcy CJ, Anversa P. 1993. Regulation of Angiotensin II Receptors on ventricular myocytes after myocardial infarction in rats. Circ Res 72:1149–1162.PubMedCrossRefGoogle Scholar
  12. 12.
    Brilla CG, Zhou G, Matsubara L, Weber KT. 1994. Collagen metabolism in cultured adult rat cardiac fibroblasts: response to angiotensin II and aldosterone. J Mol Cell Cardiol 26:809–820.PubMedCrossRefGoogle Scholar
  13. 13.
    Haywood GA, Gullestad L, Katsuya T, Hutchinson HG, Pratt RE, Horiuchi M, Fowler MB. 1997. AT1 and AT2 angiotensin receptor gene expression in human heart failure. Circulation 95:1201–1206.PubMedCrossRefGoogle Scholar
  14. 14.
    Janiak P, Pillon A, Prost JF, Vilaine JP. 1992. Role of angiotensin subtype 2 receptor in neointima formation after vascular injury. Hypertension 20:737–745.PubMedCrossRefGoogle Scholar
  15. 15.
    Viswanatan M, Saaverda JM. 1992. Expression of angiotensin II AT2 receptors in the rat skin during experimental wound healing. Peptides 13:783–786.CrossRefGoogle Scholar
  16. 16.
    Nakajima M, Hutchinson HG, Fujinaga M, Hayashida W, Morishita R, Zhang L, Horiuchi M, Pratt RE, Dzau VJ. 1995. The angiotensin II type 2 (AT2) receptor antagonizes the growth effects of the AT1 receptor: gain-of-function study using gene transfer. Proc Natl Acad Sci USA 92:10663–10667.PubMedCrossRefGoogle Scholar
  17. 17.
    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.PubMedCrossRefGoogle Scholar
  18. 18.
    Yamada T, Horiuchi M, Dzau VJ. 1996. Angiotensin II type 2 receptor mediates programmed cell death. Proc Natl Acad Sci USA 93:156–160.PubMedCrossRefGoogle Scholar
  19. 19.
    Sadoshima J, Izumo S. 1997. The cellular and molecular response of cardiac myocytes to mechanical stress. Annu Rev Physiol 59:551–571.PubMedCrossRefGoogle Scholar
  20. 20.
    Swynghedauw B, Coraboeuf E. 1994. Cardiac hypertrophy and failure. In Cardiovascular medicine. Basic aspects of myocardial function, growth, and development. Ed. JT Willerson and JN Cohn, 31–50. New York: Churchill Livingstone.Google Scholar
  21. 21.
    Waeber B, Nussberger J, Brunner HR. 1995. Angiotensin-converting enzyme inhibitors in hypertension. In Hypertension: Pathophysiology, diagnosis and management. Ed. JH Laragh and BM Brenner, 2861–2891. New York: Raven Press.Google Scholar
  22. 22.
    Guarda E, Myers PR, Brilla CG, Tyagi SC, Weber KT. 1993. Endothelial cell induced modulation of cardiac fibroblast collagen metabolism. Cardiovasc Res 27:1004–1008.PubMedCrossRefGoogle Scholar
  23. 23.
    Tsuzuki S, Matoba T, Egubhi S, Inagami T. 1996. Angiotensin II type 2 receptor inhibits cell proliferation and activates tyrosine phosphatase. Hypertension 28:916–918.PubMedCrossRefGoogle Scholar
  24. 24.
    Chassagne C, Samuel JL, Rappaport L, Meloche S. 1996. Angiotensin II AT2 Receptor activation induces expression of MKP1 and repression of mRNA encoding protooncogenes (abstract). Mol Biol Cell 7S:531a.Google Scholar
  25. 25.
    Samuel JL, Dubus I, Farhadian F, Marotte F, Oliviero P, Mercadier A, Contard F, Barrieux A, Rappaport L. 1995. Multifactorial regulation of cardiac gene expression: an in vivo and in vitro analysis. Annal NY Acad Sc 752:370–386.CrossRefGoogle Scholar
  26. 26.
    Schunkert H, Sadoshima J, Cornelius T, Kagaya Y, Weinberg EO, Izumo S, Riegger G, Lorell BH. 1995. Angiotensin II-induced growth responses in isolated adult rat hearts. Evidence for load-independent induction of cardiac protein synthesis by angiotensin II. Circ Res 76:489–497.PubMedCrossRefGoogle Scholar
  27. 27.
    Booz GW, Baker KM. 1996. Role of type 1 and type 2 angiotensin receptors in angiotensin II-induced cardiomyocyte hypertrophy. Hypertension 28(4):635–640.PubMedCrossRefGoogle Scholar
  28. 28.
    Schwartz K, Rappaport L. 1987. Isomyosins, microtubules and intermediate filaments. In the heart cell in culture. Vol. 2. Ed. A Pinson, 13–35. Boca Raton: CRC Press.Google Scholar
  29. 29.
    Dubus I, Samuel JL, Marotte F, Delcayre C, Rappaport L. 1990. β-adrenergic agonists stimulate the synthesis of non-contractile but not contractile proteins in cultured myocytes isolated from adult rat heart. Circ Res 66:867–874.PubMedCrossRefGoogle Scholar
  30. 30.
    Dubus I, Mercadier A, Lucas O, Contard F, Nallet O, Oliviero P, Rappaport L, Samuel JL. 1993. α-,β-MHC mRNA quantification in adult cardiomyocytes by in situ hybridization: effect of thyroid hormone. Am J Physiol 265:C62–C71.PubMedGoogle Scholar
  31. 31.
    Sabri A, Levy B, Poitevin P, Caputo L, Faggin E, Marotte F, Rappaport L, Samuel JL. 1997. Differential roles of AT1 and AT2 receptor subtypes in vascular trophic and phenotypic changes in response to a stimulation with angiotensin II. Arterioscler Thromb 17:257–264.CrossRefGoogle Scholar
  32. 32.
    Levy B, Benessiano J, Henrion D, Caputo L, Heymes C, Duriez M, Samuel JL. 1996. Chronic blockade of AT2-subtype receptors prevents the effect of angiotensin II on the rat cardiovascular structure. J Clin Invest 98:418–425.PubMedCrossRefGoogle Scholar
  33. 33.
    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.PubMedCrossRefGoogle Scholar
  34. 34.
    Weinberg EO, Lee MA, Weigner M, Lindpaintner K, Bishop SP, Benedict CR, Ho KK, Douglas PS, Chafizadeh E, Lorell BH. 1997. Angiotensin AT1 receptor inhibition. Effects on hypertrophic remodeling and ACE expression in rats with pressure-overload hypertrophy due to ascending aortic stenosis. Circulation 95(6):1592–1600.PubMedCrossRefGoogle Scholar
  35. 35.
    Liu YH, Yang XP, Sharov VG, Nass O, Sabbah HN, Peterson E, Carretero OA. 1997. 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 99(8): 1926–1935.PubMedCrossRefGoogle Scholar
  36. 36.
    Mulvany MJ. 1987. The structure of the resistance vasculature in essential hypertension. J Hypertension 5:129–136.CrossRefGoogle Scholar
  37. 37.
    Owens GK. 1987. Influence of blood pressure on development of aortic medial smooth muscle hypertrophy in spontaneously hypertensive rats. Hypertension 9:178–187.PubMedCrossRefGoogle Scholar
  38. 38.
    Owens GK. 1995. Regulation of differentiation of vascular smooth muscle cells. Physiol Rev 75:487–517.PubMedGoogle Scholar
  39. 39.
    Griffin SA, Brown WCB, Macpherson F, McGrath JC, Wilson VG, Korsgaard N, Mulvany MJ, Lever AF. 1991. Angiotensin II causes vascular hypertrophy in part by a non-pressor mechanism. Hypertension 17:626–635.PubMedCrossRefGoogle Scholar
  40. 40.
    Geistefer AAT, Peach MJ, Owens GK. 1988. Angiotensin II induces hypertrophy, not hyperplasia, of cultured rat aortic smooth muscle cells. Circ Res 62:749–756.CrossRefGoogle Scholar
  41. 41.
    Berk BC, Vekshtein V, Gordon HM, Tsuda T. 1989. Angiotensin II-stimulated protein synthesis in cultured vascular smooth muscle cells. Hypertension 13:305–314.PubMedCrossRefGoogle Scholar
  42. 42.
    Bardy N, Karillon GJ, Merval R, Samuel JL, Tedgui A. 1995. Differential effects of pressure and flow on DNA and protein synthesis and on fibronectin expression by arteries in a novel organ culture system. Circ Res 77:684–694.PubMedCrossRefGoogle Scholar
  43. 43.
    Bardy N, Merval R, Benessiano J, Samuel JL, Tedgui A. 1996. Pressure and Angiotensin II synergistically induce aortic fibronectin expression in organ culture model of rabbit aorta. Evidence for a pressure-induced tissue renin-angiotensin system. Circ Res 79:70–78.PubMedCrossRefGoogle Scholar
  44. 44.
    Goldberg MR, Tanaka W, Barchowsky A, Bradstreet TE, McCrea J, Lo MW, McWilliams EJ, Bjornsson TD. 1993. Effects of Losartan on blood pressure, plasma renin activity and angiotensin II in volunteers. Hypertension 21:704–713.PubMedCrossRefGoogle Scholar
  45. 45.
    Saward L, Zarhadka P. 1996. The angiotensin type 2 receptor mediates RNA synthesis in A10 vascular smooth muscle cells. J Mol Cell Cardiol 28:499–506.PubMedCrossRefGoogle Scholar
  46. 46.
    Brecher P, Chan CT, Franzblau C, Faris B, Chobabian AV. 1978. Effects of hypertension and its reversal on aortic metabolism in the rat. Circ Res 43:561–569.PubMedCrossRefGoogle Scholar
  47. 47.
    Levy BI, Michel JB, Salzmann JL, Azizi M, Poitevin P, Safar M, Camilleri JP. 1988. Effects of chronic inhibition of converting enzyme on mechanical and structural properties of arteries in rat renovascular hypertension. Circ Res 63(l):227–239.PubMedCrossRefGoogle Scholar
  48. 48.
    Pauletto P, Sarzani R, Rappelli A, Pessina AC, Sartore S. 1995. Differentiation and growth of vascular smooth muscle cells in experimental hypertension. In Hypertension: pathophysiology, diagnosis and management. Ed. JH Laragh and BM Brenner, 697–709. New York: Raven Press.Google Scholar
  49. 49.
    Sartore S, Scaneta M, Chiavegato A, Faggin E, Giuriato L, Pauletto P. 1994. Myosin isoform in smooth muscle cells during physiological and pathological vascular remodelling. J Vasc Res 31:661–681.Google Scholar
  50. 50.
    Contard F, Sabri A, Glukhova M, Sartore S, Marotte F, Pomies JP, Schiavi P, Guez D, Samuel JL, Rappaport L. 1993. Arterial smooth muscle cell phenotype in stroke-prone spontaneously hypertensive rats. Hypertension 22:665–676.PubMedCrossRefGoogle Scholar
  51. 51.
    Farhadian F, Contard F, Corbier A, Barrieux A, Rappaport L, Samuel JL. 1995. Fibronectin expression during physiological and pathological cardiac growth. J Mol Cell Cardiol 27:981–990.PubMedCrossRefGoogle Scholar
  52. 52.
    Samuel JL, Barrieux A, Dufour S, Dubus I, Contard F, Koteliansky V, Farhadian F, Marotte F, Thiéry JP, Rappaport L. 1996. Accumulation of fetal fibronectin mRNAs during the development of rat cardiac hypertrophy induced by pressure overload. J Clin Invest 88:1737–1746.CrossRefGoogle Scholar
  53. 53.
    Siragy HM, Carey RM. 1996. The subtype 2 (AT2) angiotensin receptor regulates renal cyclic guanosine 3′-5′-monophosphate and AT1 receptor-mediated prostaglandin E2 production in conscious rats. J Clin Invest 97:1978–1982.PubMedCrossRefGoogle Scholar
  54. 54.
    Nakajima M, Hutchinson HG, Fujinaga M, Hayashida W, Morishita R, Zhang L, Horiuchi M, Pratt RE, Dzau VJ. 1995. The angiotensin II type 2 (AT2) receptor antagonizes the growth effects of the AT1 receptor: Gain-of-function study using gene transfer. Proc Natl Acad Sci USA 92:10663–10667.PubMedCrossRefGoogle Scholar
  55. 55.
    Corda S, Mebazaa A, Gandolfini MP, Fitting C, Marotte F, Peynet J, Charlemagne D, Cavaillon JM, Payen D, Rappaport L, Samuel JL. 1997. Trophic effect of human pericardial fluid on adult cardiac myocytes—Differential role of fibroblast growth factor-2 and factors related to ventricular hypertrophy. Circ Res 81:679–687.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • K. Sabri
    • 1
  • C. Chassagne
    • 1
  • B. Lévy
    • 1
  • J.L. Samuel
    • 1
  • L. Rappaport
    • 1
  1. 1.INSERM U 127, INSERM U141, IFR CirculationUniversité D. DiderotFrance

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