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Cardiac Mechanotransduction pp 106–119Cite as

The Role of Adrenoceptors in Mechanotransduction

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Abstract

Adrenoceptors are a large family of seven membrane spanning G-protein coupled receptors involved in many regulatory processes of the heart. Under conditions of mechanical load to heart, i.e., pressure overload, an activation of the sympathetic nerve system leads direcdy to stimulation of receptors of this family. Especially α-adrenoceptors are constantly coupled to regulation of protein synthesis and their stimulation leads to an imbalance of protein synthesis and degradation causing myocardial hypertrophy. Moreover, events initially evoked by coactivation of the renin-angiotensin-system, including the activation of cytokines like TGF-β, are able to induce an additional coupling of β2-adrenoceptors to the regulation of protein synthesis, further favouring an imbalance of protein synthesis and degradation. Thus, several adrenoceptors are involved in a complex network of external and internal signals, finally leading to an adaptive response of the heart to mechanical load. The present review summarises our current understanding of these signal transduction pathways and their contribution to myocardial hypertrophy and heart failure.

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References

  1. Rapaccioulo A, Esposito G, Caron K et al. Important role of endogenous norepinpehrine and epinephrine in the development on in vivo pressure overload cardiac hypertrophy. J Am Coll Cardiol 2001; 38:876–882.

    Article  Google Scholar 

  2. Michel MC, Kenny B, Schwinn DA. Classification of α1-adrenoceptor subtypes. Naunyn-Schmiedeberg’s Arch Pharmacol 1995; 352:1–10.

    Article  CAS  Google Scholar 

  3. Price DT, Chari RS, Berkowitz DE et al. Expression of α1-adrenergic receptor subtype mRNA in rat tissues and human SK-N-MC neuronal cells: Implications for α1-adrenergic receptor subclassification. Mol Pharmacol 1994; 46:221–226.

    PubMed  CAS  Google Scholar 

  4. Morgan HE, Baker KM. Cardiac hypertrophy mechanical, neural and endocrine dependence. Circulation 1991; 83:13–25.

    PubMed  CAS  Google Scholar 

  5. Zierhut W, Zimmer HG. Significance of myocardial α-and β-adrenoceptors in catecholamine-induced cardiac hypertrophy. Circ Res 1989; 65:14717–1425.

    Google Scholar 

  6. Fuller SJ, Gaitanaki CJ, Sugden PH. Effects of catecholamines on protein synthesis in cardiac myocytes and perfused hearts isolated from adult rats. Biochem J 1990; 266:727–736.

    PubMed  CAS  Google Scholar 

  7. Simpson PC. Stimulation of hypertrophy of cultures neonatal rat hearts cells through an α1-adrenergic receptor and induction of beating through an α1-and β1-adrenergic receptor interaction: Evidence for independent regulation of growth and beating. Circ Res 1985; 56:884–894.

    PubMed  CAS  Google Scholar 

  8. Ardati A, Nemer M. A nuclear pathway for α1-adrenergic receptor signalling in cardiac cells. EMBO J 1993; 12:5131–5139.

    PubMed  CAS  Google Scholar 

  9. Waspe LE, Ordahl CP, Simpson PC. The cardiac β-myosin heavy chain isogene is induced selectively in α1-adrenergic receptor-stimulated hypertrophy of cultured rat heart myocytes. J Clin Invest 1990; 85:1206–1214.

    PubMed  CAS  Google Scholar 

  10. Long CS, Ordahl CP, Simpson PC. α1-Adrenergic receptor stimulation of sarcomeric actin isogene transcription in hypertrophy of cultured rat heart muscle cells. J Clin Invest 1989; 83:1078–1082.

    PubMed  CAS  Google Scholar 

  11. Schlüter K-D, Piper HM. Trophic effects of catecholamines and parathyroid hormone on adult ventricular cardiomyocytes. Am J Physiol Heart Circ Physiol 1992; 263:H1739–H1746.

    Google Scholar 

  12. Pinson A, Schlüter K-D, Zhou XJ et al. α-and β-Adrenergic stimulation of protein synthesis in cultured adult ventricular cardiomyocytes. J Mol Cell Cardiol 1993; 25:477–490.

    Article  PubMed  CAS  Google Scholar 

  13. Ikeda UY, Tsuruya Y, Yaginuma T. α1-Adrenergic stimulation is coupled to cardiac myocyte hypertrophy. Am J Physiol Heart Circ Physiol 1991; 260:H953–H956.

    CAS  Google Scholar 

  14. Knowlton KU, Michel MC, Itani M et al. The α1-adrenoceptor subtype mediates biochemical, molecular, and morphological features of cultured myocardial cell hypertrophy. J Biol Chem 1993; 268:15374–15380.

    PubMed  CAS  Google Scholar 

  15. Pönicke K, Schlüter K-D, Heinroth-Hoffmann I et al. Noradrenalin-induced increase in protein synthesis in adult rat cardiomyocytes: Involvement of only α1A-adrenoceptors. Naunyn-Schmiedeberg’s Arch Pharmacol 2001; 364:444–453.

    Article  CAS  Google Scholar 

  16. Mier K, Kemken D, Katus HA et al. Adrenergic activation of cardiac phospholipase D: Role of α1-adrenoceptor subtypes. Cardiovasc Res 2002; 54:133–139.

    Article  PubMed  CAS  Google Scholar 

  17. Rokosh DG, Stewart AF, Chang KC et al. α1-Adrenergic receptor subtype mRNAs are differentially regulated by α1-adrenergic and other hypertrophic stimuli in cardiac myocytes in culture and in vivo. Repression of α1B and α1D but not of α1C. J Biol Chem 1996; 271:5839–5843.

    Article  PubMed  CAS  Google Scholar 

  18. Deng XF, Sculptoreanu A, Mulay S et al. Crosstalk between α1A-and α1B-adrenoceptors in neonatal rat myocardium: Implications in cardiac hypertrophy. J Pharmacol Exptl Therap 1998; 286:489–196.

    CAS  Google Scholar 

  19. O’Connell TD, Stigwart PM, Simpson GL et al. α1-Adrenergic receptors are required for stress response in the heart. Circulation 2002; 106(Suppl):II-58, [Abstract].

    Google Scholar 

  20. Iaccarino G, Keys JR, Rapacciuolo A et al. Regulation of myocardial βARK1 expression in catecholamine-induced cardiac hypertrophy in transgenic mice overexpressing α1B-adrenergic receptors. J Am Coll Cardiol 2001; 38:534–540.

    Article  PubMed  CAS  Google Scholar 

  21. Grupp IL, Lorenz JN, Walsh RA et al. Overexpression of α1B-adrenergic receptor induces left ventricular dysfunction in the absence of hypertrophy. Am J Physiol Heart Circ Physiol 1998; 275:H1338–H1350.

    CAS  Google Scholar 

  22. Milano CA, Dolber PC, Rockman HA et al. Myocardial expression of a constitutively active α1B-adrenergic receptor in transgenic mice induces cardiac hypertrophy. Proc Natl Acad Sci USA 1994; 91:10109–10113.

    Article  PubMed  CAS  Google Scholar 

  23. Vecchione C, Fratta L, Tizzoni D et al. Cardiovascular influences of α1B-adrenergic receptor deficient mice. Circ 2002; 105:1700–1707.

    Article  CAS  Google Scholar 

  24. Lin F, Owens WA, Chen S et al. Targeted α1A-adrenergic receptor overexpression induces enhanced cardiac contractility but not hypertrophy. Circ Res 2001; 89:343–350.

    Article  PubMed  CAS  Google Scholar 

  25. Sabri A, Pak E, Allcott SA et al. Coupling function of endogenous α1-and β-adrenergic receptors in mouse cardiomyocytes. Circ Res 2000; 86:1047–1053.

    PubMed  CAS  Google Scholar 

  26. Imai C, Tozawa M, Sunagawa O et al. Alterations in α1-adrenergic receptor densities in right and left ventricles of spontaneously hypertensive rats. Biol Pharm Bull 1995; 18:1001–1005.

    PubMed  CAS  Google Scholar 

  27. Kagiya T, Hori M, Iwakura K et al. Role of increased α1-adrenergic activity in cardiomyopathic Syrian hamster. Am J Physiol Heart Circ Physiol 1991; 260:H80–H88.

    CAS  Google Scholar 

  28. Böhm M, Mende U, Schmitz U et al. Increased sensitivity to α-adrenoceptor stimulation but intact purinergic and muscarinergic effects in prehypertensive cardiac hypertrophy of spontaneously hypertensive rats. Naunyn-Schmiedeberg’s Arch Pharmacol 1986; 333:284–289.

    Article  Google Scholar 

  29. Ganguly PK, Lee SL, Beamish RE et al. Altered sympathetic system and adrenoceptors during the development of cardiac hypertrophy. Am Heart J 1989; 118:520–525.

    Article  PubMed  CAS  Google Scholar 

  30. Izumi Y, Matsuoka M, Kubo A et al. Prevention of cardiac hypertrophy by a sub-antihypertensive dose of the α1-adrenergic antagonist bunazosin in Dahl salt-sensitive rats. Hypertens Res 1996; 19:147–150.

    PubMed  CAS  Google Scholar 

  31. Schobel HP, Langenfeld M, Gatzka C et al. Treatment and post-treatment effects of α-versus β-receptor blockers on left ventricular structure and function in essential hypertension. Am Heart J 1996; 132:1004–1009.

    Article  PubMed  CAS  Google Scholar 

  32. Veelken R, Schmieder RE. Overview of α1-adrenoceptor antagonism and recent advances in hypertensive therapy. Am J Hypertens 1996; 9:S139S–149S.

    Article  Google Scholar 

  33. D’Angelo DD, Sakata Y, Lorenz JN et al. Transgenic Gαq overexpression induces cardiac contractile failure in mice. Proc Natl Acad Sci USA 1997; 94:8121–8126.

    Article  PubMed  CAS  Google Scholar 

  34. Wettschureck N, Rütten H, Zywietz A et al. Absence of pressure overload induced myocardial hypertrophy after conditional inactivation of Gαq/Gα11 in cardiomyocytes. Nat Med 2001; 7:1236–1240.

    Article  PubMed  CAS  Google Scholar 

  35. Fujita T, Toya Y, Iwatsubo K et al. Accumulation of molecules involved in α1-adrenergic signal within caveolae: Caveolin expression and the development of cardiac hypertrophy. Cardiovasc Res 2001; 51:709–716.

    Article  PubMed  CAS  Google Scholar 

  36. Bowman JC, Steinberg SF, Jiang T. Expression of protein kinase C β in the heart causes hypertrophy in adult mice and sudden death in neonates. J Clin Invest 1997; 100:2189–2195.

    PubMed  CAS  Google Scholar 

  37. Schäfer M, Schäfer C, Piper HM et al. Hypertrophic responsiveness of cardiomyocytes to α-and β-adrenoceptor stimulation requires sodium-proton-exchanger-1 (NHE-1) activation but not cellular alkalization. Eur J Heart Failure 2002; 4:249–254.

    Article  Google Scholar 

  38. Ruf S, Piper HM, Schlüter K-D. Specific role for the extracellular signal-regulated kinase pathway in angiotensin II-but not in phenylephrine-induced cardiac hypertrophy in vitro. Pflügers Arch Eur J Physiol 2002; 443:483–490.

    Article  CAS  Google Scholar 

  39. Rohde S, Sabri S, Kamasamudran R et al. The α1-adrenoceptor subtype and protein kinase C isoform-dependence of norepinephrine’s actions in cardiomyocytes. J Mol Cell Cardiol 2000; 32:1193–1209.

    Article  PubMed  CAS  Google Scholar 

  40. Sadoshima J, Qui Z, Morgan JP et al. Angiotensin II and other hypertrophic stimuli mediated by G protein-coupled receptors activate tyrosine kinase, mitogen-activated protein kinase, and 90-kD S6 kinase in cardiac myocytes. The critical role of Ca2+-dependent signalling. Circ Res 1995; 76:1–55.

    PubMed  CAS  Google Scholar 

  41. Bolouyt-MO, Zheng JS, Younes A et al. Rapamycin inhibits α1-adrenergic receptor-stimulated cardiac myocyte hypertrophy but not activation of hypertrophiy-associated genes. Evidence for involvement of p70 S6 kinase. Circ Res 1997; 81:176–182.

    Google Scholar 

  42. Schlüter K-D, Goldberg Y, Taimor G et al. Role of phosphatidylinositol 3-kinase activation in the hypertrophic growth of adult ventricular cardiomyocytes. Cardiovasc Res 1998; 40:174–181.

    Article  PubMed  Google Scholar 

  43. Matsui T, Li L, Wu JC et al. Phenotypic spectrum caused by transgenic overexpression of activated Akt in the heart. J Biol Chem 2002; 277:22896–22901.

    Article  PubMed  CAS  Google Scholar 

  44. McDermott PJ, Rothblum LI, Smith SD et al. Accelerated rates of ribososmal RNA synthesis during growth of contracting heart cells in culture. J Biol Chem 1989; 264:18220–18227.

    PubMed  CAS  Google Scholar 

  45. Kanevskij M, Taimor G, Schäfer M. Neuropeptide Y modifies the hypertrophic response of adult ventricular cardiomyocytes to norepinephrine. Cardiovasc Res 2002; 53:879–887.

    Article  PubMed  CAS  Google Scholar 

  46. Glennon PE, Kaddoura S, Sale EM et al. Depletion of mitogen-activated protein kinase using antisense oligonucleotide approach downregulates the phenylephrine-induced hypertrophic response in rat cardiac myocytes. Circ Res 1996; 78:954–961.

    PubMed  CAS  Google Scholar 

  47. Thorborn J, Frost JA, Thorburn A. Mitogen-activated protein kinase mediate changes in gene expression, but not cytoskeletal organization associated with cardiac muscle cell hypertrophy. J Cell Biol 1994; 126:1565–1572.

    Article  Google Scholar 

  48. Schlüter K-D, Simm A, Schäfer M et al. Early response kinase and PI 3-kinase activation in adult cardiomyocytes and their role in hypertrophy. Am J Physiol Heart Circ Physiol 1999; 276:H1655–H1663.

    Google Scholar 

  49. Wang L, Proud CG. Ras/Erk signalling is essential for activation of protein synthesis by Gq protein-coupled receptor agonists in adult cardiomyocytes. Circ Res 2002; 91:821–829.

    Article  PubMed  CAS  Google Scholar 

  50. Xiao L, Pimental DR, Amin JK et al. MEK1/2-ERK1/2 mediates α1-adrenergic receptor-stimulated hypertrophy in adult rat ventricular myocytes. J Mol Cell Cardiol 2001; 33:779–787.

    Article  PubMed  CAS  Google Scholar 

  51. Post GR, Swiderski C, Waldrop BA et al. Guanine nucleotide exchange factor-like factor (Rfl) induces gene expression and potentiates α1-adrenergic receptor-induced transcriptional responses in neonatal rat ventricular myocytes. J Biol Chem 2002; 277:15286–15292.

    Article  PubMed  CAS  Google Scholar 

  52. Amin JK, Xiao L, Pimental DR et al. Reactive oxygen species mediate α-adrenergic receptor-stimulated hypertrophy in adult rat ventricular myocytes. J Mol Cell Cardiol 2001; 33:131–139.

    Article  PubMed  CAS  Google Scholar 

  53. Eble DM, Qi M, Waldschmidt S et al. Contractile activity is required for sarcomeric assembly in phenylephrine-induced cardiac myocyte hypertrophy. Am J Physiol 1998; 274:C1226–1237.

    PubMed  CAS  Google Scholar 

  54. Hein L, Altman JD, Kobilka BK. Two functionally distinct α2-adrenergic receptors regulate sympathetic neurotransmission. Nature 1999; 402:181–184.

    Article  PubMed  CAS  Google Scholar 

  55. Brede M, Wiesmann F, Jahns R et al. Feedback inhibition of catecholamine release by two different α2-adrenoceptor subtypes prevents progression of heart failure. Circ 2002; 106:2491–2496.

    Article  CAS  Google Scholar 

  56. Schäfer M, Frischkopf K, Taimor G et al. Hypertrophic effect of selective β1-adrenoceptor stimulation on ventricular cardiomyocytes from adult rat. Am J Physiol Cell Physiol 2000; 279:C495–C503.

    PubMed  Google Scholar 

  57. Schäfer M, Pönicke K, Heinroth-Hoffmann I et al. β-Adrenoceptor stimulation attenuates the hypertrophic effect of α-adrenoceptor stimulation in adult rat ventricular cardiomyocytes. J Am Coll Cardiol 2001; 37:300–307.

    Article  PubMed  Google Scholar 

  58. Wang Y, Huang S, Sah VP et al. Cardiac muscle cell hypertrophy and apoptosis induced by distinct members of the p38 mitogen-activated protein kinase family. J Biol Chem 1998; 273:2161–2168.

    Article  PubMed  CAS  Google Scholar 

  59. Crespo P, Cachero TG, Xu N et al. Dual effect of β-adrenergic receptors on mitogen-activated protein kinase. Evidence for a βγ-dependent activation of a Gαs-cAMP-mediated inhibition. J Biol Chem 1995; 270:25259–25265.

    Article  PubMed  CAS  Google Scholar 

  60. Engelhardt S, Hein L, Keller U et al. Inhibition of Na+-H+ exchange prevents hypertrophy, fibro-sis, and heart failure in β1-adrenergic receptor transgenic mice. Circ Res 2002; 90:814–819.

    Article  PubMed  CAS  Google Scholar 

  61. Bisognano JD, Weinberg HD, Bohlmeyer TJ et al. Myocardial-directed overexpression of the human β1-adrenergic receptor in transgenic mice. J Mol Cell Cardiol 2000; 32:817–830.

    Article  PubMed  CAS  Google Scholar 

  62. Iwata M, Yoshikawa T, Baba A et al. Autoimmunity against the second extracellular loop of β1-adrenergic receptors induces β-adrenergic receptor desensitisation and myocardial hypertrophy in vivo. Circ Res 2001; 88:578–586.

    PubMed  CAS  Google Scholar 

  63. Leineweber K, Heinroth-Hoffmann I, Pönicke K et al. Cardiac β-adrenoceptor desensitization due to increased β-adrenoceptor kinase activity in chronic uremia. J Am Soc Nephrol 2002; 13:117–124.

    PubMed  CAS  Google Scholar 

  64. Mondry A, Bourgeois F, Carre F et al. Decrease in β1-adrenergic and M2-muscarinic receptor mRNA levels and unchanged accumulation of mRNAs coding for Gαi-2 and Gαs proteins in rat cardiac hypertrophy. J Mol Cell Cardiol 1995; 27:2287–2294.

    Article  PubMed  CAS  Google Scholar 

  65. Galinier M, Senard JM, Valet P et al. Cardiac β-adrenoceptors and adenylyl cyclase activity in human left ventricular hypertrophy due to pressure overload. Fundam Clin Pharmacol 1994; 8:90–99.

    Article  PubMed  CAS  Google Scholar 

  66. Böhm M, Kirchmayr R, Erdmann E. Myocardial Giα-protein levels in patients with hypertensive cardiac hypertrophy, ischemic heart disease and cardiogenic shock. Cardiovasc Res 1995; 30:611–618.

    Article  PubMed  Google Scholar 

  67. Asai K, Yang GP, Geng YJ et al. β-Adrenergic receptor blockade arrests myocyte damage and preserves cardiac function in the transgenic Gsα mouse. J Clin Invest 1999; 104:551–558.

    Article  PubMed  CAS  Google Scholar 

  68. Dubus I, Samuel JL, Marotte F et al. β-Adrenergic agonists stimulate the synthesis of noncontractile but not contractile proteins in cultured myocytes isolated from adult rat hearts. Circ Res 1990; 66:867–874.

    PubMed  CAS  Google Scholar 

  69. Zhou XJ, Schlüter K-D, Piper HM. Hypertrophic responsiveness to β2-adrenoceptor stimulation on adult ventricular cardiomyocytes. Mol Cell Biochem 1996; 163/164:211–216.

    Article  CAS  Google Scholar 

  70. Simm A, Schlüter K-D, Diez C et al. Activation of p70 s6 kinase by β-adrenoceptor agonists on adult cardiomyocytes. J Mol Cell Cardiol 1998; 30:2059–2067.

    Article  PubMed  CAS  Google Scholar 

  71. Xiao RP. β-Adrenergic signalling in the heart: Dual coupling of the p2-adrenergic receptor to Gs and Gi protein. Sci STKE 2001; RE15.

    Google Scholar 

  72. Schlüter K-D, Frischkopf K, Flesch M et al. Central role for ornithine decarboxylase in β-adrenoceptor mediated hypertrophy. Cardiovasc Res 2000; 45:410–417.

    Article  PubMed  Google Scholar 

  73. Nakano M, Kanda T, Matsuzaki S et al. Effect of losartan, an AT1 selective angiotensin II receptor antagonist, on isoproterenol-induced cardiac ornithine decarboxylase activity. Res Commun Mol Pathol Pharmacol 1995; 88:21–30.

    PubMed  CAS  Google Scholar 

  74. Du XJ, Autelitano DJ, Dilley RJ et al. β2-Adrenergic receptor overexpression exacerebrates development of heart failure after aortic stenosis. Circulation 2000; 101:71–77.

    PubMed  CAS  Google Scholar 

  75. Murphy RJ, Beliveau L, Gardiner PF et al. Nifedipine does not impede clenbuterol-stimulated muscle hypertrophy. Proc Soc Exp Biol Med 1999; 221:184–187.

    Article  PubMed  CAS  Google Scholar 

  76. Wong K, Boheler KR, Petrou M et al. Pharmacological modulation of pressureinduced cardiac hypertrophy: Changes in ventricular function, extracellular matrix, and gene expression. Circulation 1997; 96:2239–2246.

    PubMed  CAS  Google Scholar 

  77. Schlüter K-D, Zhou XJ, Piper HM. Induction of hypertrophic responsiveness to isoproterenol by TGF-β in adult rat cardiomyocytes. Am J Physiol Cell Physiol 1995; 269:C1311–C1316.

    Google Scholar 

  78. Taimor G, Schlüter K-D, Frischkopf K et al. Autocrine regulation of TGFβ expression in adult cardiomyocytes. J Mol Cell Cardiol 1999; 31:2127–2136.

    Article  PubMed  CAS  Google Scholar 

  79. Wenzel S, Taimor G, Piper HM et al. Redox-sensitive intermediates mediate angiotensin II-induced p38 MAP kinase activation, AP-1 binding activity, and TGF-β expression in adult ventricular cardiomyocytes. FASEB J 2001; 15:2291–2293.

    PubMed  CAS  Google Scholar 

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  1. Physiologisches Institut, Aulweg 129, 35392, Giessen, Germany

    Klaus-Dieter Schlüter, Hans Michael Piper & Sibylle Wenzel

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  1. Klaus-Dieter Schlüter
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Schlüter, KD., Piper, H.M., Wenzel, S. (2007). The Role of Adrenoceptors in Mechanotransduction. In: Cardiac Mechanotransduction. Springer, New York, NY. https://doi.org/10.1007/978-0-387-48868-4_7

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