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


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.



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.


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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

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