Autonomic contribution to endothelin-1 increase during laboratory anger-recall stress in patients with coronary artery disease.
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.
Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, Connecticut, USA. mb2358@columbia.edu
Matthew M
MM
Burg
Aaron
A
Soufer
Rachel
R
Lampert
Dorothea
D
Collins
Robert
R
Soufer
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000368:Aged; D000786:Anger / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000378:metabolism; D003324:Coronary Artery Disease / Q000235:genetics / Q000378:metabolism* / Q000523:psychology*; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D011939:Mental Recall / Q000502:physiology*; D008875:Middle Aged; D015999:Multivariate Analysis
D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D019332:Endothelin-1
Circulation. 1990 Jul;82(1):188-95
2194695
N Engl J Med. 1991 Nov 28;325(22):1551-6
1944439
Exp Biol Med (Maywood). 2005 Oct;230(9):652-8
16179733
Am J Physiol. 1970 Apr;218(4):1030-7
5435400
Circulation. 2001 Sep 4;104(10):1114-8
11535565
N Engl J Med. 1999 Jan 14;340(2):115-26
9887164
Circulation. 1995 Nov 1;92(9):2426-31
7586341
Biochem Biophys Res Commun. 1993 Mar 31;191(3):1081-8
8466485
Life Sci. 2005 Oct 7;77(21):2723-34
15978638
J Am Coll Cardiol. 2010 Feb 16;55(7):637-42
20170788
J Am Coll Cardiol. 2003 Aug 20;42(4):698-704
12932604
Eur J Pharmacol. 1999 Jan 1;364(1):65-73
9920186
Circulation. 1996 Nov 15;94(10):2402-9
8921780
J Exp Med. 1990 Dec 1;172(6):1741-8
1701822
J Cardiovasc Electrophysiol. 2005 Apr;16(4):372-7
15828878
Circulation. 2000 Jan 18;101(2):158-64
10637203
Circulation. 1991 Apr;83(4 Suppl):II43-51
2009629
J Am Coll Cardiol. 1993 Aug;22(2):440-8
8335813
Am Heart J. 2004 May;147(5):e21
15131556
Circulation. 2002 Oct 1;106(14):1800-5
12356633
Can J Physiol Pharmacol. 2003 Jun;81(6):570-7
12839268
Circulation. 1995 Feb 15;91(4):941-7
7850978
Int J Mol Med. 2008 Aug;22(2):149-53
18636167
Mol Med. 2007 Mar-Apr;13(3-4):178-84
17592552
Am Heart J. 2004 Aug;148(2):e10
15309013
Circulation. 1996 Mar 1;93(5):1043-65
8598068
N Engl J Med. 2008 Jan 31;358(5):475-83
18234752
N Engl J Med. 1991 Oct 3;325(14):997-1001
1886637
Ann Intern Med. 1993 Mar 15;118(6):429-32
8439117
Circulation. 2000 Nov 14;102(20):2473-8
11076819
Am J Cardiol. 2003 Jan 15;91(2):137-42
12521623
Resuscitation. 2002 Apr;53(1):71-6
11947982
Nature. 2002 Dec 19-26;420(6917):853-9
12490958
J Clin Invest. 1990 Feb;85(2):587-90
2153712
Neuroscience. 2002;115(1):275-83
12401340
Lancet. 2000 Jul 22;356(9226):310-1
11071190
Br J Pharmacol. 1995 Dec;116(8):3309-15
8719812
Mol Pharmacol. 1999 May;55(5):902-9
10220569
Circ Res. 1994 Jul;75(1):85-96
8013087
Chest. 2005 May;127(5):1474-6
15888812
Heart. 2006 Aug;92(8):1035-40
16399852
J Appl Physiol (1985). 2007 Sep;103(3):1007-11
17626836
Pharmacol Ther. 2006 Aug;111(2):508-31
16457892
Clin Exp Rheumatol. 1997 Mar-Apr;15(2):163-7
9196868
Circulation. 2002 Jun 18;105(24):2817-20
12070106
J Nucl Cardiol. 2005 Sep-Oct;12(5):523-9
16171711