Autonomic contribution to endothelin-1 increase during laboratory anger-recall stress in patients with coronary artery disease

Mol Med. 2011 May-Jun;17(5-6):495-501. doi: 10.2119/molmed.2010.00083. Epub 2011 Jan 19.


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% CI 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology*
  • Aged
  • Anger / physiology*
  • Blood Pressure / drug effects
  • Catecholamines / metabolism
  • Coronary Artery Disease / genetics
  • Coronary Artery Disease / metabolism*
  • Coronary Artery Disease / psychology*
  • Endothelin-1 / genetics
  • Endothelin-1 / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Heart Rate / drug effects
  • Humans
  • Male
  • Mental Recall / physiology*
  • Middle Aged
  • Multivariate Analysis


  • Adrenergic beta-Antagonists
  • Catecholamines
  • Endothelin-1