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Changes in adrenergic receptors during the development of heart failure

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Moderate and severe stages of congestive heart failure due to the loss of myocardium upon coronary occlusion in rats was associated with an increase in alpha-adrenergic receptors and a decrease in beta-adrenergic receptors in the viable left ventricle. However, at early stages of heart failure the number of beta-adrenergic receptors was decreased without any changes in the number of alpha-adrenergic receptors. The affinities of these receptors to alpha receptor antagonist (3H-prazosin) and beta receptor antagonist (3H-dihydroalprenolol) were not altered in the failing hearts. On the other hand, the pattern of changes in both alpha- and beta-adrenergic receptors in heart membranes treated with oxygen free radical generating system was different from that seen in the failing hearts. In particular, the affinities for these receptors were decreased whereas the number of beta-receptors was increased and the number of alpha-receptors was decreased or unchanged. These results indicate that alterations in the adrenergic receptors in heart failure are not due to the formation of oxygen free radicals.

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  1. 1.

    Dhalla NS, Ziegelhoffer A, Harrow JAC: Regulatory role of membrane systems in heart function. Can J Physiol Pharmacol 55: 1211–1234, 1977

  2. 2.

    Dhalla NS, Dixon IMC, Beamish RE: Biochemical basis of heart function and contractile failure. J Appl Cardiol 6: 7–30, 1991

  3. 3.

    Bristow MR, Ginsburg R, Miobe W, Cubicciotti RS, Sageman WS, Lurie K, Billingham ME, Harrison DC, Stinson EB: Decreased catecholamine sensitivity and β-adrenergic-receptor density in failing human hearts. N Engl J Med 307: 205–211, 1982

  4. 4.

    Homcy CJ, Vatner SF, Vatner DE: β-adrenergic receptor regulation in the heart in pathophysiologic states: Abnormal adrenergic responses in cardiac disease. Annu Rev Physiol 53: 137–159, 1991

  5. 5.

    Lee HR: α-adrenergic receptors in heart failure. Heart Failure 5: 62–70, 1989

  6. 6.

    Dixon IMC, Dhalla NS: Alterations in cardiac adrenoceptors in congesive heart failure secondary to myocardial infarction. Coronary Artery Disease 2: 805–814, 1991

  7. 7.

    Staton HC, Brenner G, Mayfield ED: Studies on isoproterenolinduced cardiomegaly in rats. Am Heart J 77: 72–80, 1969

  8. 8.

    Laks MM, Morady F, Swan BA, Swan HJC: Myocardial hypertrophy produced by chronic infusion of subhypertensive doses of norepinephrine in the dog. Chest 64: 75–79, 1973

  9. 9.

    Simpson P: Norepinephrine-stimulated hypertrophy of cultured rat myocardial cells in an α1-adrenergic response. J Clin Invest 72: 732–738, 1983

  10. 10.

    Zierhut W, Zimmer HG: Significance of myocardial α- and β-adrenoceptors in catecholamine-induced cardiac hypertrophy. Circ Res 65: 1417–1425, 1989

  11. 11.

    Tsien RW: Cyclic AMP and contractile activity in the heart. Adv Cyclic Nucl Res 8: 363–420, 1977

  12. 12.

    Berridge MJ: Inositol triphosphate and diacylglycerol: Two interacting second messengers. Annu Rev Biochem 56: 159–193, 1987

  13. 13.

    Fan THM, Liang CS, Kawashima S, Banerjee SP: Alterations in cardiac β-adrenoceptors responsiveness and adenylate cyclase system by congestive heart failure in dogs. Eur J Pharmacol 140: 123–132, 1987

  14. 14.

    Denniss AR, Colcucci WS, Allen PD, Marsh D: Distribution and function of human ventricular β-adrenergic receptors in congestive heart failure. J Mol Cell Cardiol 21: 651–660, 1989

  15. 15.

    Denniss AR, Marsh JD, Quigg RJ, Gordon JB, Colucci WS: β-adrenergic receptor number and adenylate cyclase function in denervated transplanted and cardiomyopathic human hearts. Circulation 79: 1028–1034, 1989

  16. 16.

    Fowler MB, Laser JA, Hopkins GL, Minobe W, Bristow MR: Assessment of the β-adrenergic receptor pathway in the intact failing human heart: Progressive receptor down-regulation and subsensitivity to agonist response. Circulation 74: 1290–1302, 1986

  17. 17.

    Ponleur H, Rousseau MF, Hanel C, Marlow HF, Charlier AA: Left ventricular sensitivity to β-adrenoceptor stimulating drugs in patients with ischemic heart disease and varying degrees of ventricular dysfunction. Circ Res 61 (Suppl 1): 91–95, 1987

  18. 18.

    Steinfath M, Geertz B, Schmitz W, Scholz H, Haverich A, Breil I, Hanrath P, Renupcke C, Sigmund M, Lo HB: Distinct downregulation of cardiac β1- and β2-adrenoceptors in different human diseases. Naunyn Schmiedebergs Arch Pharmacol 343: 217–220, 1991

  19. 19.

    Galinier M, Senard JM, Valet P, Brean G, Planat V, Arias A, Tran MA, Montastruc JL: Myocardial hypertrophy, cardiac β-adrenoceptors and adenylate cyclase activity during sinoaortic denervation in dogs. Br J Pharmacol 105: 341–346, 1992

  20. 20.

    Marzo KP, Frey MJ, Wilson JR, Liang BT, Manning DR, Lanoce V, Molinoff PB: β-adrenergic receptor-G protein-adenylate cyclase complex in experimental canine congestive heart failure produced by rapid ventricular pacing. Circ Res 69: 1546–1556, 1991

  21. 21.

    Karliner JS, Barnes P, Brown M, Dollery C: Chronic heart failure in the guinea pig increases cardiac α- and β-adrenoceptors. Eur J Pharmacol 67: 115–118, 1980

  22. 22.

    Fu LX, Sjogren KG, Liang QM, Waagsten F, Hoebeke J, Hjalmarson A: Activity of receptors coupled to guanine nucleotide binding regulatory protein in doxorubicin induced cardiomyopathy. Cardiovasc Res 25: 145–150, 1991

  23. 23.

    Vatner DE, Vatner SF, Fujii AM, Homcy CJ: Loss of high affinity cardiac β-adrenergic receptors in dogs with heart failure. J Clin Invest 76: 2259–2264, 1985

  24. 24.

    Karliner JS, Alabaster C, Stephens H, Barnes P, Dillery C: Enhanced noradrenaline response in cardiomyopathic hamsters: Possible relation to changes in adrenoceptors studied by radioligand binding. Cardiovasc Res 15: 296–304, 1981

  25. 25.

    Kagijay T, Hori M, Iwakura K, Iwai K, Watanabe Y, Uchida S, Yoshida H, Kitabatake A, Inove M, Kamada T: Role of increased α-adrenergic activity in cardiomyopathic Syrian hamsters. Am J Physiol 260: H80-H88, 1991

  26. 26.

    Sen L, Liang BT, Colucci WS, Smith TW: Enhanced α1-adrenergic responsiveness in cardiomyopathic hamster cardiac myocytes: Relation to the expression of pertussis toxin-sensitive G protein and α1-adrenergic receptors. Circ Res 67: 1182–1192, 1990

  27. 27.

    Bristow MR, Minobe W, Ramussen R, Hershberger RE, Hoffman BB: α1-Adrenergic receptors in the non-failing and failing heart. J Pharmacol Exp Therap 247: 1039–1045, 1988

  28. 28.

    Vago T, Bevilacqua M, NMorbiato G, Baldi G, Caebat E, Bertora P, Baroli G, Accinori R: Identification of α-adrenergic receptors on sarcolemma from normal subjects and patients with idiopathic dilated cardiomyopathy: Characteristics and linkage to GTP-binding protein. Circ Res 64: 474–481, 1989

  29. 29.

    Wolff AA, Hines DK, Karliner JS: Refined membrane preparations mask ischemic fall in myocardial β-receptor density. Am J Physiol 257: 111032–111036, 1989

  30. 30.

    Marsh JD, Sweeney KA: β-Adrenergic receptor regulation during hypoxia in intact cultured heart cells. Am J Physiol 256: 11275–11281, 1989

  31. 31.

    Maisel AS, Motulsky HJ, Ziegler MG, Insel PA: Ischemia- and angonist induced changes in α- and β-adrenergic receptor traffic in guinea pig heart. Am J Physiol 253: 111159–111166, 1987

  32. 32.

    Coor PB, Shayman JA, Karmer JB, Kipnis RJ: Increased aadrenergic receptors in ischemic cat myocardium: A potential mediator of electrophysiological derangements. J Clin Invest 67: 1232–1236, 1980

  33. 33.

    Clozel JP, Holck M, Osterrieder W, Burkard W, Daprada M: Effects of chronic myocardial infarction on responsiveness to isoprenaline and the state of myocardial β-adrenoceptors in rats. Cardiovasc Res 21: 688–695, 1987

  34. 34.

    Vleeming W, Van der Wouw PA, de Biesebeck JD, van Rooj HH, Wemer J, Porsus AJ: Density of β-adrenoceptors in rat heart and lymphocytes 48 hr and 7 days after acute myocardial infarction. Cardiovasc Res 23: 859–866, 1989

  35. 35.

    Bauman G, Reiss G, Erhardt WD, Felix SB, Ludwig L, Blunel G, Blomer H: Impaired β-adrenergic stimulation in the uninvolved ventricle post-acute myocardial infarction: Reversible defect due to excessive circulating catecholamine-induced decline in number and affinity of β-receptors. Am Heart J 101: 569–581, 1981

  36. 36.

    Karliner JS, Stevens M, Grattan M, Wolosyn W, Honbo N, Hoffman JE: β-adrenergic receptor properties of canine myocardium: Effect of chronic myocardial infarction. J Am Coll Cardiol 8: 349–356, 1986

  37. 37.

    Gupta M, Singal PK: Higher antioxidant capacity during chronic stable heart hypertrophy. Circ Res 64: 398–406, 1989

  38. 38.

    Singal PK, Kirshenbaum LA: A relative deficit in antioxidant reserve may contribute in cardiac failure. Can J Cardiol 6: 47–49, 1990

  39. 39.

    Kaneko M, Chapman DC, Ganguly PK, Beamish RE, Dhalla NS: Modification of cardiac adrenergic receptors by oxygen free radicals. Am J Physiol 260: 11821–11826, 1991

  40. 40.

    Schinke I, Haberland A, Will-Shahabe L, Kuttner I, Papier B: In vitro effects of reactive OZ species on the β-receptor-adenylyl cyclase system. Mol Cell Biochem 110: 41–46, 1992

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Correspondence to Naranjan S. Dhalla.

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Dhalla, N.S., Dixon, I.M.C., Suzuki, S. et al. Changes in adrenergic receptors during the development of heart failure. Mol Cell Biochem 114, 91–95 (1992). https://doi.org/10.1007/BF00240302

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Key words

  • beta-adrenoceptors
  • alpha-adrenoceptors
  • heart failure
  • free radicals
  • heart membranes