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Activation of the neuroendocrine response in heart failure: Adaptive or maladaptive process?

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Summary

Congestive heart failure is a clinical syndrome in which the capacity of the heart to maintain cardiac output is impaired. As a consequence, blood pressure is threatened and endocrine and paracrine mechanisms are activated to preserve circulatory homeostasis and to maintain blood pressure. At terminal stages, a complex multiorgan syndrome develops with severe pump failure, intense systemic vasoconstriction, and avid water and sodium retention. Increasing evidence points to humoral circulating or locally synthesized substances as one of the causes of the terminal consequences of heart failure. Therefore, the hypothesis that the syndrome of heart failure is, at least in part, a humoral disease has developed and is obtaining scientific credibility. Consequently, the neuroendocrine response to heart failure is no longer viewed as a compensatory beneficial mechanism. Instead, we have learned through the years that pharmacological treatment aimed at reducing the effect of the neuroendocrine response is indeed clinically and prognostically advantageous for the patient.

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References

  1. Ferrari, R. Neuroendocrine response to heart failure. In: Ostadal, B, Dhalla, NS, eds. Heart Function in Health and Disease. Boston: Kluwer Academic Publishers, 1993: 307–320.

    Google Scholar 

  2. Harris, P. Role of arterial pressure in the edema of heart disease. Lancet 1988:May 7; 1(8593);1036–1038.

    Google Scholar 

  3. Harris, P. Evolution and the cardiac patient. Cardiovasc Res 1983;313:373–437.

    Google Scholar 

  4. Braunwald, E. Pathophysiology of heart failure. In: Braunwald, E, ed. Heart Disease. A Textbook of Cardiovascular Medicine, 4th ed. Philadelphia: WB Saunders, 1992: 393–418.

    Google Scholar 

  5. Packer, M, Lee, WH, Kessler, PD, et al. Role of neurohormonal mechanisms in determining survival in patients with severe chronic heart failure. Circulation 1987;75(Supp. IV): IV80.

    Google Scholar 

  6. Poole-Wilson, PA. Heart failure. Med Interne 1985;2: 866–871.

    Google Scholar 

  7. Anand, IS, Ferrari, R, Kalra, GS, et al. Edema of cardiac origin: Studies of body water and sodium, renal function, hemodynamics and plasma hormones in untreated congestive cardiac failure. Circulation 1989;80:209–305.

    Google Scholar 

  8. Anand, IS, Chandrashekhar, Y, Ferrari, R, et al. Pathogenesis of the congestive state in chronic obstructive pulmonary disease: Studies of body water and sodium, renal function, hemodynamics, and plasma hormones during edema and after recovery. Circulation 1992;86:12–21.

    Google Scholar 

  9. Anand, IS, Ferrari, R, Kalra, GS, et al. Pathogenesis of edema in constrictive pericarditis: Studies of body water and sodium, renal function, hemodynamics and plasma hormones before and after pericardiectomy. Circulation 1991; 83:1880–1887.

    Google Scholar 

  10. Ferrari, R, Anand, IS. Neurohumoral changes in untreated heart failure. Cardiovasc Drugs Ther 1989;3:979–986.

    Google Scholar 

  11. Chidsey, CA, Harrison, DC, Braunwald, E. The augmentation of plasma norepinephrine response to exercise in patients with congestive heart failure. N Engl J Med 1962; 267:650–654.

    Google Scholar 

  12. Goldstein, DS. Plasma norepinephrine as an indicator of sympathetic neural activity in clinical cardiology. Ann J Cardiol 1981;48:1147–1152.

    Google Scholar 

  13. Francis, GS, Cohn, JN. The autonomic nervous system in congestive heart failure. Ann Rev Med 1986;37:235–247.

    Google Scholar 

  14. Francis, GS, Rector, TS, Cohn, JN. Sequential neurohumoral measurements in patients with congestive heart failure. Am Heart J 1988;116:1464–1468.

    Google Scholar 

  15. Francis, GS, Goldsmith, SR, Pierpont, G, Cohn, JN. Free and conjugated plasma catecholamines in patients with congestive heart failure. J Lab Clin Med 1984;103:393–398.

    Google Scholar 

  16. Rutenberg, HL, Spann, JFJr. Alterations of cardiac sympathetic neurotransmitter activity in congestive heart failure. In: Mason, DT, ed. Congestive Heart Failure: Mechanism, Evaluation and Treatment. New York: Dun-Donnelley, 1976.

    Google Scholar 

  17. Chidsey, CA, Braunwald, E, Morrow, AG. Catecholamine excretion and cardiac stores of norepinephrine in congestive heart failure. Ann J Med 1965;39:442–451.

    Google Scholar 

  18. Chidsey, CA, Sonnenblick, EH, Morrow, AG, Braunwald, E. Norepinephrine stores and contractile force of papillary muscle from the failing heart. Circulation 1966;33:43–51.

    Google Scholar 

  19. Spean, JF, Chidsey, CA, Pool, PE, Braunwald, E. Mechanism of norepinephrine depletion in experimental heart failure produced by aortic constriction in the guinea pig. Circ Res 1965;17:312–321.

    Google Scholar 

  20. Ceconi C, Condorelli E, Rodella A, et al. Effect of cardiac failure in rats on myocardial concentrations of noradrenaline and on arterial ANP, bombesin- and neurotensin-like immunoreactivity. International Symposium: Physiology, Clinical Aspects and Treatment of Coronary Insufficiency, Torino, 3–6 June 1986, p. 16.

  21. Harris, P. Congestive cardiac failure: Central role of the arterial blood pressure. Br Heart J 1987;58:190–203.

    Google Scholar 

  22. Packer, M. Neurohormonal interactions and adaptations in congestive heart failure. Circulation 1988;77:721–730.

    Google Scholar 

  23. Lipkin, DP, Poole-Wilson, PA. Treatment of chronic heart failure: A review of recent trials. Br Med J 1985;291: 993–996.

    Google Scholar 

  24. Swedberg, K, Hjalmarson, A, Waagstein, F, Wallentin, I. Beneficial effects of long-term beta-blockade in congestive cardiomyopathy. Br Heart J 1980;66(2):117–133.

    Google Scholar 

  25. Packer, M. The fact of carvedilol on morbidity and mortality in patients with chronic heart failure. N Engl J Med 1996; 23:1349–1355.

    Google Scholar 

  26. Hirsch, AT, Dzau, VJ, Creager, MA. Baroreceptor function in congestive heart failure: Effect on neurohormonal activation and regional vascular resistance. Circulation 1987; 75(Suppl. IV):IV36.

    Google Scholar 

  27. Tsutamoto, T, Kanamori, T, Morigami, N, et al. Possibility of down regulation of atrial natriuretic peptide receptor coupled to guanylate cyclase in peripheral vascular beds of patients tients with chronic severe heart failure. Circulation 1993; 87:70–75.

    Google Scholar 

  28. Fowler, MB, Laser, JA, Hopkins, GL, et al. Assessment of beta-adrenergic receptor pathway in the intact failing human heart: Progressive receptor down-regulation and subsensitivity to agonist response. Circulation 1986;74: 1290–1299.

    Google Scholar 

  29. Bristow, MR, Ginsburg, R, Minobe, W. Decreased catecholamine sensitivity and beta-adrenergic-receptor density in failing human hearts. N Engl J Med 1982;307:205–211.

    Google Scholar 

  30. Bristow, MR, Minobe, W, Rasmussen, et al. β adrenergic neuroeffector abnormalities in the failing human heart are produced by local rather than systemic mechanisms. J Clin Invest 1992;89:803–815.

    Google Scholar 

  31. Kramer, PS, Mason, DT, Braunwald, E. Augmented sympathetic neurotransmitter activity in the peripheral vascular bed of patients with congestive heart failure and cardiac norepinephrine depletion. Circulation 1968;38:629–639.

    Google Scholar 

  32. Brown, JJ, Davies, DL, Johnson, VW, et al. Resin relationships in congestive cardiac failure, treated and untreated. Am Heart J 1970;80:329–342.

    Google Scholar 

  33. Bayliss, J, Norell, M, Canepa Anson, R, et al. Untreated heart failure: Clinical and neuroendocrine effects of introducing diuretics. Br Heart J 1987;57:17–22.

    Google Scholar 

  34. Packer, M. The neurohumoral hypothesis: A theory to explain the mechanism of disease progression in heart failure. J Am Coll Cardiol 1992;20:248–254.

    Google Scholar 

  35. Skinner, SL, McCubbin, JW, Page, JH. Control of resin secretion. Circ Res 1964;15:64–76.

    Google Scholar 

  36. Ferrari, R, Ceconi, C, DeGiuli, F, et al. Temporal relations of the endocrine response to hypotension with sodium nitroprusside. Cardioscience 1992;3:51–59.

    Google Scholar 

  37. Watkins, LJr, Burton, JA, Haber, E, et al. The reninaldosterone system in congestive failure on conscious dogs. J Clin Invest 1976;57:1606–1607.

    Google Scholar 

  38. Weber, KT, Anversa, P, Armstrong, PW, et al. Remodeling and reparation of the cardiovascular system. J Am Coll Cardiol 1992;20:3–16.

    Google Scholar 

  39. The Captopril Multicenter Research Group. A placebo-controlled trial of captopril in refractory chronic congestive heart failure. J Am Coll Cardiol 1983;2:755–763.

    Google Scholar 

  40. Cleland, JGF, Dargie, HJ, Bal, SG, et al. Effects of enalapril in heart failure: A double blind study of effects on exercise performance, renal function, hormones and metabolic state. Br Heart J 1985;54:305–312.

    Google Scholar 

  41. Riegger, GAJ. The effects of ACE inhibitors on exercise capacity in the treatment of congestive heart failure. J Cardiovasc Pharmacol 1990;15:S41-S46.

    Google Scholar 

  42. The CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure: Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). N Engl J Med 1987;316:1429–1435.

    Google Scholar 

  43. Cohn, JN, Hohnson, G, Ziesche, S, et al. A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure. N Engl J Med 1991;352:303–310.

    Google Scholar 

  44. Cleland, JG, Dargie, HJ, Hodsman, GP, et al. Captopril in heart failure: A double-blind controlled trial. Br Heart J 1984;52:530–535.

    Google Scholar 

  45. The SOLVD Investigators: Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med 1991;325: 293–302.

    Google Scholar 

  46. The SOLVD Investigators: Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. N Engl J Med 1992;327:685–691.

    Google Scholar 

  47. Ceconi, C, Benigno, M, Mazzoletti, A, et al. Aldosteronel level: Its role in heart failure. In: Ferrari, R, ed. Aldosterone in Congestive Heart Failure. Venice: Canal Press, 1995:47–55.

    Google Scholar 

  48. Riegger, GAJ, Liebau, G, Kochsiek, K. Antidiuretic hormone in congestive heart failure. Am J Med 1982;72:49–61.

    Google Scholar 

  49. DeBold, AJ. Heart atrial granularity. Effects of changes in water electrolyte balance. Proc Soc Exp Biol Med 1979;161: 508–511.

    Google Scholar 

  50. Atlas, SA, Kleinert, HD, Camargo, MJ. Purification, sequencing and synthesis of natriuretic and vasoactive rat atrial peptide. Nature 1984;309:717–719.

    Google Scholar 

  51. DeBold, AJ, Borenstein, HB, Veress, AT, Sonnenberg, H. A rapid and potent natriuretic response to intravenous injection of atrial myocardial extract in rats. Life Sci 1981;28: 89–94.

    Google Scholar 

  52. Agnoletti, G, Rodella, A, Ferrari, R, Harris, P. Release of atrial natriuretic peptide-like immunoreactive material during stretching of the rat atrium in vitro. J Mol Cell Cardiol 1987;19:217–220.

    Google Scholar 

  53. Agnoletti, G, Curello, S, Ceconi, C, et al. Effects of isoproterenol (I) on the release of atrial natriuretic peptide (ANP) from isolated atria. Am J Cardiovasc Pathol 1992;4: 203–209.

    Google Scholar 

  54. Laragh, JH. Atrial natriuretic hormone, the reninangiotensin axis, and blood pressure-electrolyte homeostasis. N Engl J Med 1985;313:1330–1343.

    Google Scholar 

  55. Shaknovitch, A, Pondolfino, K, Clark, M, et al. Atrial natriuretic factor in normal subjects and heart failure patients: Plasma levels and renal, hormonal, and hemodynamic responses to peptide infusion. J Clin Invest 1986;78: 1362–1373.

    Google Scholar 

  56. Ferrari, R, Ceconi, C, Curello, S, Visioli, O. Biochemical abnormalities underlying myocardial failure. In: Dagianti, A, Feigenbaum, H, eds. Echocardiography. Amsterdam: Excerpta Medica, Elsevier Science, 1990:125–130.

    Google Scholar 

  57. Suzuki, E, Hirata, Y, Kohmoto, O, et al. Cellular mechanisms for synthesis and secretion of atrial natriuretic peptide and brain natriuretic peptide in cultured rat atrial cells. Circ Res 1992;71:1039–1048.

    Google Scholar 

  58. Perrella, MA, Margulies, KB, Burnett, JCJr. Atrial natriuretic factor in congestive heart failure: Physiologic role of therapeutic implications. In: Adnot, S, Cantin, M, Chambrier, PE, eds. Atrial Natriuretic Factor: Physiological and Clinical Aspects. Paris: Medicine-Sciences Flammarion, 1991.

    Google Scholar 

  59. Lerman, A, Burnett, JCJr. Intact and altered endothelium in regulation of vasomotion. Circulation 1992;82(Suppl. 3): III12-III19.

    Google Scholar 

  60. Levine, B, Kalman, J, Mayer, L, et al. Elevated circulating levels of tumor necrosis factor in severe chronic heart failure. N Engl J Med 1990;323:236–241.

    Google Scholar 

  61. Balligand, JL, Ungureanu, D, Kelly, RA, et al. Abnormal contractile function due to induction of nitric oxide synthesis in rat cardiac myocytes follows exposure to activated macrophage-conditioned medium. J Clin Invest 1993;91: 2314–2319.

    Google Scholar 

  62. Yokoyama, T, Vaca, L, Rossen, RD, et al. Cellular basis for the negative inotropic effects of tumor necrosis factor-alpha in the adult mammalian heart. J Clin Invest 1993;92: 2303–2312.

    Google Scholar 

  63. Eichenholz, PW, Eichacker, PW, Hoffman, WD, et al. Tumor necrosis factor challenges in canines: Patterns of cardiovascular dysfunction. Am J Physiol 1992;263:H668-H675.

    Google Scholar 

  64. Walley, KR, Hebert, PC, Wakai, Y, et al. Decrease in left ventricular contractility after tumor necrosis factor-alpha infusion in dogs. J Appl Physiol 1994;76:1060–1067.

    Google Scholar 

  65. Katz, SD, Rao, R, Berman, JW, et al. Pathophysiological correlates of increased serum tumor necrosis factor in patients with congestive heart failure. Circulation 1994;90:12–16.

    Google Scholar 

  66. Harris, P. Role of arterial pressure in the edema of heart disease. Lancet 1988; May 7; 1(8593):1036–1038.

    Google Scholar 

  67. Harris, P. Evolution and the cardiac patient. Cardiovasc Res 1983;313:373–437.

    Google Scholar 

  68. Harris, P. Biology of cardiac failure. Eur Heart J 1982; 3(Suppl. D):5–10.

    Google Scholar 

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Ferrari, R., Ceconi, C., Curello, S. et al. Activation of the neuroendocrine response in heart failure: Adaptive or maladaptive process?. Cardiovasc Drug Ther 10 (Suppl 2), 623–629 (1996). https://doi.org/10.1007/BF00052509

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