Advertisement

Molecular Medicine

, Volume 17, Issue 5–6, pp 495–501 | Cite as

Autonomic Contribution to Endothelin-1 Increase during Laboratory Anger-Recall Stress in Patients with Coronary Artery Disease

  • Matthew M Burg
  • Aaron Soufer
  • Rachel Lampert
  • Dorothea Collins
  • Robert Soufer
Research Article

Abstract

In coronary artery disease (CAD), endothelin-1 (ET-1) is released by activated macrophages and thereby contributes to coronary plaque rupture and triggered cardiac events. The multifactorial regulation of ET-1 includes stimulated release by cytokines and autonomic factors. Laboratory stress provokes alteration in autonomic tone and prolonged ET-1 mediated endothelial dysfunction. The objective of the study is to determine the autonomic contribution to an increase in ET-1 in response to laboratory stress in patients with CAD. Patients (n = 88) with chronic stable CAD instrumented with hemodynamic monitor, digital electrocardiogram (ECG) monitor and indwelling catheter for blood sampling completed a laboratory protocol that included initial rest (30 min), baseline (BL: 10 min), and anger recall stress (AR: 8 min). Change from BL to AR was determined for (a) parasympathetic activity (by spectral analysis of ECG); (b) sympathetic activity (by circulating catecholamines); and (c) ET-1. AR provoked increases from BL in catecholamines, and a decrease in parasympathetic activity. Multivariate analysis with change in parasympathetic activity and catecholamines, while controlling for age and use of β-blockers, revealed a significant odds ratio (OR = 3.27, 95% Cl 1.03, 10.41 P = 0.04) for an increase in ET-1 associated with parasympathetic withdrawal; no other variables were significant. The predominant influence of parasympathetic activity on anger/stress-provoked increase in ET-1 is consistent with the cholinergic antiinflammatory pathway. Future examination of autonomic influences on atherosclerotic leukocytes, endothelial cell function and the dynamics of ET-1 are warranted.

Notes

Acknowledgments

This work was supported by R01 awards from the National Heart, Lung, and Blood Institute to MB (HL84438) and A Soufer (HL59619 and HL071116) and by a Merit Review award from the Department of Veterans Affairs to A Soufer.

References

  1. 1.
    Ehrenreich H, et al. (1990) Endothelins, peptides with potent vasoactive properties, are produced by human macrophages. J.Exp. Med. 172:1741–8.CrossRefGoogle Scholar
  2. 2.
    Lerman A, et al. (1991) Circulating and tissue en-dothelin immunoreactivity in advanced atherosclerosis. N. Engl. J. Med. 325:997–1001.CrossRefGoogle Scholar
  3. 3.
    Winkles JA, Alberts GF, Brogi E, Libby P. (1993) Endothelin-1 and endothelin receptor mRNA expression in normal and atherosclerotic human arteries. Biochem. Biophys. Res. Commun. 191:1081–8.CrossRefGoogle Scholar
  4. 4.
    Zeiher AM, Goebel H, Schachinger V, Ihling C. (1995) Tissue endothelin-1 immunoreactivity in the active coronary atherosclerotic plaque. A clue to the mechanism of increased vasoreactivity of the culprit lesion in unstable angina. Circulation. 91:941–7.CrossRefGoogle Scholar
  5. 5.
    McClellan G, Weisberg A, Rose D, Winegrad S. (1994) Endothelial cell storage and release of endothelin as a cardioregulatory mechanism. Circ. Res. 75:85–96.CrossRefGoogle Scholar
  6. 6.
    Zeiher AM, Goebel H, Schachinger V, Ihling C. (1995) Tissue endothelin-1 immunoreactivity in the active coronary atherosclerotic plaque. A clue to the mechanism of increased vasoreactivity of the culprit lesion in unstable angina. Circulation. 91:941–7.CrossRefGoogle Scholar
  7. 7.
    Zhang X, et al. (2008) Circadian rhythm disorder of thrombosis and thrombolysis-related gene expression in apolipoprotein E knock-out mice. Int. J. Mol. Med. 22:149–53.PubMedGoogle Scholar
  8. 8.
    Khan IA. (2005) Role of endothelin-1 in acute myocardial infarction. Chest. 127:1474–6.CrossRefGoogle Scholar
  9. 9.
    Taylor AJ, et al. (2004) Myocardial endothelin-1 release and indices of inflammation during an-gioplasty for acute myocardial infarction and stable coronary artery disease. Am. Heart J. 148:e10.CrossRefGoogle Scholar
  10. 10.
    Wilbert-Lampen U, et al. Modified serum profiles of inflammatory and vasoconstrictive factors in patients with emotional stress-induced acute coronary syndrome during World Cup Soccer 2006. J. Am. Coll. Cardiol. 2010:55:637–42.CrossRefGoogle Scholar
  11. 11.
    Woods M, et al. (1999) Endothelin-1 is induced by cytokines in human vascular smooth muscle cells: evidence for intracellular endothelin-converting enzyme. Mol. Pharmacol. 55:902–9.PubMedGoogle Scholar
  12. 12.
    Kahaleh MB, Fan PS. (1997) Effect of cytokines on the production of endothelin by endothelial cells. Clin. Exp. Rheumatol. 15:163–7.PubMedGoogle Scholar
  13. 13.
    Kinlay S, et al. (2001) Role of endothelin-1 in the active constriction of human atherosclerotic coronary arteries. Circulation. 104:1114–8.CrossRefGoogle Scholar
  14. 14.
    Brunner F, Bras-Silva C, Cerdeira AS, Leite-Moreira AF. (2006) Cardiovascular endothelins: Essential regulators of cardiovascular homeostasis. Pharmacol. Ther.111:508–31.CrossRefGoogle Scholar
  15. 15.
    Lavallee M, Thorin E. (2003) Role of ET-1 in the regulation of coronary circulation. Can. J. Physiol. Pharmacol. 81:570–7.CrossRefGoogle Scholar
  16. 16.
    Tracey KJ. (2002) The inflammatory reflex. Nature. 420:853–9.CrossRefGoogle Scholar
  17. 17.
    Petrov T, Steiner J, Braun B, Rafols JA. (2002) Sources of endothelin-1 in hippocampus and cortex following traumatic brain injury. Neuroscience. 115:275–83.CrossRefGoogle Scholar
  18. 18.
    Yang ZH, et al. (1990) Threshold concentrations of endothelin-1 potentiate contractions to norepi-nephrine and serotonin in human arteries. A new mechanism of vasospasm? Circulation. 82:188–95.CrossRefGoogle Scholar
  19. 19.
    Wilbert-Lampen U, et al. (2008) Cardiovascular events during World Cup soccer. N. Eng. J. Med. 358:475–83.CrossRefGoogle Scholar
  20. 20.
    Strike PC, Perkins-Porras L, Whitehead DL, McEwan J, Steptoe A. (2006) Triggering of acute coronary syndromes by physical exertion and anger: clinical and sociodemographic characteristics. Heart. 92:1035–40.CrossRefPubMedCentralGoogle Scholar
  21. 21.
    Goldberg AD, et al. (1996) Ischemic, hemodynamic, and neurohormonal responses to mental and exercise stress. Experience from the Psychophysiological Investigations of Myocardial Ischemia Study (PIMI). Circulation. 94:2402–9.CrossRefGoogle Scholar
  22. 22.
    Lampert R, Jain D, Burg MM, Batsford WP, McPherson CA. (2000) Destabilizing effects of mental stress on ventricular arrhythmias in patients with implanted cardioverter-defibrillators. Circulation. 101:151–64.CrossRefGoogle Scholar
  23. 23.
    Pagani G, et al. (1991) Sympathovagal interaction during mental stress: a study using spectral analysis of heart rate variability in healthy control subjects and patients with a prior myocardial infarction. Circulation. 83:43–51.Google Scholar
  24. 24.
    Burg MM, Vashist A, Soufer R. (2005) Mental stress ischemia: present status and future goals. J. Nucl. Cardiol. 12:523–9.CrossRefGoogle Scholar
  25. 25.
    Burg MM, Jain D, Soufer R, Kerns RD, Zaret BL. (1993) Role of behavioral and psychological factors in mental stress-induced silent left ventricular dysfunction in coronary artery disease. J. Am. Coll. Cardiol. 22:440–8.CrossRefGoogle Scholar
  26. 26.
    Yeung AC, et al. (1991) The effect of atherosclerosis on the vasomotor response of coronary arteries to mental stress. N. Engl. J. Med. 325:1551–6.CrossRefGoogle Scholar
  27. 27.
    Arrighi JA, et al. (2000) Myocardial blood flow response to mental stress in normal subjects and patients with chronic coronary artery disease. Lancet. 356:310–11.CrossRefGoogle Scholar
  28. 28.
    Ghiadoni L, et al. (2000) Mental stress induces transient endothelial dysfunction in humans. Circulation. 102:2473–8.CrossRefGoogle Scholar
  29. 29.
    Spieker LE, et al. (2002) Mental stress induces prolonged endothelial dysfunction via endothelin-A receptors. Circulation. 105:2817–20.CrossRefGoogle Scholar
  30. 30.
    Lampert R, et al. (2002) Emotional and physical precipitants of ventricular arrhythmia. Circulation. 106:1800–5.CrossRefGoogle Scholar
  31. 31.
    Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. (1996) Heart rate variability: standards of measurement, physiological interpretation, and clinical use. Circulation. 93:1043–65.CrossRefGoogle Scholar
  32. 32.
    Lampert R, Ickovics JR, Viscoli CJ, Horwitz RI, Lee FA. (2003) Effects of propranolol on recovery of heart rate variability following acute myocardial infarction and relation to outcome in the Beta-Blocker Heart Attack Trial. Am. J. Cardiol. 91:137–42.CrossRefGoogle Scholar
  33. 33.
    Lampert R, et al. (2005) Effects of psychologic stress on repolarization and relationship to auto-nomic and hemodynamic factors. J. Cardiovasc. Electrophysiol. 16:372–7.CrossRefGoogle Scholar
  34. 34.
    Katona PG, Poitras JW, Barnett GO, Terry BS. (1970) Cardiac vagal efferent activity and heart period in the carotid sinus reflex. Am. J. Physiol. 218:1030–7.PubMedGoogle Scholar
  35. 35.
    Wagner A, et al. (2002) Plasma endothelin in patients with acute aortic disease. Resuscitation. 53:71–6.CrossRefGoogle Scholar
  36. 36.
    Griffiths KA, Sader MA, Skilton MR, Harmer JA, Celermajer DS. (2003) Effects of raloxifene on endothelium-dependent dilation, lipoproteins, and markers of vascular function in postmenopausal women with coronary artery disease. J. Am. Coll. Cardiol. 42:698–704.CrossRefGoogle Scholar
  37. 37.
    Lerman A, et al. (1995) Endothelin in coronary endothelial dysfunction and early atherosclerosis in humans. Circulation. 92:2426–31.CrossRefGoogle Scholar
  38. 38.
    Kinlay S, et al. (2001) Role of endothelin-1 in the active constriction of human atherosclerotic coronary arteries. Circulation. 104:1114–8.CrossRefGoogle Scholar
  39. 39.
    Ross R. (1999) Atherosclerosis—an inflammatory disease. N. Engl. J. Med. 340:115–26.CrossRefGoogle Scholar
  40. 40.
    Sloan RP, et al. (2007) RR interval variability is inversely related to inflammatory markers: the CARDIA study. Mol. Med. 13:178–84.PubMedPubMedCentralGoogle Scholar
  41. 41.
    Sloan RP, et al. (2007) Aerobic exercise attenuates inducible TNF production in humans. J. Appl. Physiol. 103:1007–11.CrossRefGoogle Scholar
  42. 42.
    Jurca R, Church TS, Morss GM, Jordan AN, Earnest CP. (2004) Eight weeks of moderate intensity exercise training increases heart rate variability in sedentary postmenopausal women. Am. Heart J. 147:e8–15.CrossRefGoogle Scholar
  43. 43.
    Tuomainen P, Peuhkurninen K, Kettunen R, Rauramaa R. (2005) Regular physical exercise, heart rate variability and turbulence in a 6-year randomized controlled trial in middle aged men: the DNASCO study. Life Sci. 77:2723–34.CrossRefGoogle Scholar
  44. 44.
    Hohlfeld T, et al. (1995) The contribution of tumour necrosis factor-alpha and endothelin-1 to the increase of coronary resistance in hearts from rats treated with endotoxin. Br. J. Pharmacol. 116:3309–15.CrossRefPubMedCentralGoogle Scholar
  45. 45.
    Wahl JR, et al. (2005) Murine macrophages produce endothelin-1 after microbial stimulation. Exp. Biol. Med. 230:652–8.CrossRefGoogle Scholar
  46. 46.
    Mitsutomi N, Akashi C, Odagiri J, Matsumura Y. (1999) Effects of endogenous and exogenous nitric oxide on endothelin-1 production in cultured vascular endothelial cells. Eur. J. Pharmacol. 364:65–73.CrossRefGoogle Scholar
  47. 47.
    Boulanger C, Luscher TF. (1990) Release of endothelin from the procine aorta. Inhibition by endothelium-derived nitric oxide. J.Clin. Invest. 85:587–90.CrossRefPubMedCentralGoogle Scholar
  48. 48.
    Rushmer RF. (1989) Structure and function of the cardiovascular system. In: Weiss SM, Schneider-man N, Kaufmann PG (eds). Handbook of research methods in cardiovascular behavioral medicine. Plenum, New York, pp. 5–22.CrossRefGoogle Scholar
  49. 49.
    Polderman KH, et al. (1993) Influence of sex hormones on plasma endothelin levels. Ann. Intern. Med. 118:429–32.CrossRefGoogle Scholar

Copyright information

© The Feinstein Institute for Medical Research 2011

Authors and Affiliations

  • Matthew M Burg
    • 1
    • 2
    • 3
  • Aaron Soufer
    • 1
  • Rachel Lampert
    • 1
  • Dorothea Collins
    • 2
  • Robert Soufer
    • 1
    • 2
  1. 1.Section of Cardiovascular MedicineYale University School of Medicine/VA ConnecticutWest HavenUSA
  2. 2.Veterans Administration Connecticut Healthcare SystemWest Haven CampusWest HavenUSA
  3. 3.Center for Behavioral Cardiovascular HealthColumbia University School of MedicineNew York CityUSA

Personalised recommendations