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

作者：Burg Matthew M^*; Soufer Aaron; Lampert Rachel; Collins Dorothea; Soufer Robert

来源：Molecular Medicine, 2011, 17(5-6): 495-501.

DOI：10.2119/molmed.2010.00083

In coronary artery disease (CAD), endothelin-1 (ET-1) is released by activated macrophages and thereby contributes to coronory 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, wh le controlling for age and use of beta-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 examinotion of autonomic influences on atherosclerotic leukocytes, endothelial cell function and the dynamics of ET-1 are warranted.

• 出版日期2011-6