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Endothelial function |

Close relation of endothelial function in the human coronary and peripheral circulations FREE

Todd J. Anderson, MD; Akimi Uehata, MD; Marie D. Gerhard, MD; Ian T. Meredith, MBBS, PhD; Sarah Knab, BA; Danielle Delagrange, BS, MS; Eric H. Lieberman, MD; Peter Ganz, MD, FACC; Mark A. Creager, MD, FACC; Alan C. Yeung, MD, FACC; Andrew P. Selwyn, MD, FACC
[+] Author Information

Present address and address for correspondence: Dr. Todd J. Anderson, 8th Floor, Foothills Hospital, 1403-29th Street NW, Calgary, Alberta. Canada T2N-2T9.

This study was supported by a Clinical Fellowship of the Alberta Heritage Foundation for Medical Research, Edmonton, Canada (Dr. Anderson); the National Defense Medical College of Japan, Tokyo, Japan (Dr. Uehata); a National Heart Foundation of Australia Ralph Reader Overseas Research Fellowship, Melbourne, Australia (Dr. Meredith); and the following awards from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland: Academic Award in Systemic and Pulmonary Vascular Medicine HL-02663 (Dr. Creager), Clinician-Investigator Development Award I K08 HL-02787 (Dr. Yeung), Research Career Development Award 1 K04 HL-02566 and N1H 5P01 HL 48743 (Dr. Ganz) and R01 HL-38780-05 (Dr. Selwyn).

American College of Cardiology

J Am Coll Cardiol. 1995;26(5):1235-1241. doi:10.1016/0735-1097(95)00327-4
Published online

Objectives.  The relation between endothelium-dependent vasodilator function in the brachial and coronary arteries was determined in the same subjects.

Background.  Coronary artery endothelial dysfunction precedes the development of overt atherosclerosis and is important in its pathogenesis. A noninvasive assessment of endothelial function in a peripheral conduit vessel, the brachial artery, was recently described, but the relation between brachial artery function and coronary artery vasodilator function has not been explored.

Methods.  In 50 patients referred to the catheterization laboratory for the evaluation of coronary artery disease (mean age ± SD 56 ± 10 years), the coronary vasomotor response to serial intracoronary infusions of the endothelium-dependent agonist acetylcholine (10−8 to 10−6 mol/liter), was studied. Endotheliumdependent vasodilation was also assessed in the brachial artery by measuring the change in brachial artery diameter in response to reactive hyperemia.

Results.  Patients with coronary artery endothelial dysfunction manifested as vasoconstriction in response to acetylcholine had significantly impaired flow-mediated vasodilation in the brachial artery compared with that of patients with normal coronary endothelial function (4.8 ± 5.5% vs. 10.8 ± 7.6%, p < 0.01). Patients with coronary artery disease also had an attenuated brachial artery vasodilator response compared with that of patients with angiographically smooth coronary arteries (4.5 ± 4.6% vs. 9.7 ± 8.1%, p < 0.02). By multivariate analysis, the strongest predictors of reduced brachial dilator responses to flow were baseline brachial artery diameter (p < 0.001), coronary endothelial dysfunction (p = 0.003), the presence of coronary artery disease (p = 0.007) and cigarette smoking (p = 0.016). The brachial artery vasodilator response to sublingual nitroglycerin was independent of coronary endothelial responses or the presence of coronary artery disease. The positive predictive value of abnormal brachial dilation (<3%) in predicting coronary endothelial dysfunction is 95%.

Conclusions.  This study demonstrated a close relation between coronary artery endothelium-dependent vasomotor responses to acetylcholine and flow-mediated vasodilation in the brachial artery. This noninvasive method may become a useful surrogate in assessing the predisposition to atherosclerosis in patients with cardiac risk factors.

References

Moncada  S, Higgs  A; The l-arginine-nitric oxide pathway. N Engl J Med. 329 1993:2002-2012.
CrossRef | PubMed
Meredith  IT, Yeung  AC, Weidinger  FF; Role of impaired endotheliumdependent vasodilation in ischemic manifestations of coronary artery disease. Circulation. 87 (Suppl V) 1993:V
Ludmer  PL, Selwyn  AP, Shook  TL; Paradoxical vasoconstriction induced by acetylcholine in atherosclerosic coronary arteries. N Engl J Med. 315 1986:1046-1051.
CrossRef | PubMed
Zeiher  AM, Drexler  H, Wollschläger  H, Just  H; Modulation of coronary vasomotor tone in humans: progressive endothelial dysfunction with different stages of coronary atherosclerosis. Circulation. 83 1991:391-401.
CrossRef | PubMed
Yasue  H, Matsuyama  K, Okumura  K, Morikami  Y, Ogawa  H; Responses of angiographically normal human coronary arteries to intracoronary injection of acetylcholine by age and segment: possible role of early coronary atherosclerosis. Circulation. 81 1990:482-490.
CrossRef | PubMed
(Pt 2)Lefroy  DC, Crake  T, Uren  NG, Davies  GJ, Maseri  A; Effects of nitric oxide in the human coronary circulation. Circulation. 88 1993:I
CrossRef
Vita  JA, Treasure  CB, Nabel  EG; The coronary vasomotor response to acetylcholine relates to risk factors for coronary artery disease. Circulation. 81 1990:491-497.
CrossRef | PubMed
[abstract]Dyce  MC, Anderson  TJ, Orav  J; The relationship between endothelial vasodilator function and LDL particle size, density and number in human coronary atherosclerosis. (Pt 2) Circulation. 88 1993:1-466.
Leung  W-H, Lau  C-P, Wong  C-K; Beneficial effect of cholesterol-lowering on coronary endothelium-dependent relaxation in hypercholsterolaemic patients. Lancet. 341 1993:1496-1500.
CrossRef | PubMed
Poll  U, Holtz  J, Busse  R, Bassenge  E; Crucial role of endothelium in the vasodilator response to increased flow in vivo. Hypertension. 8 1986:37-44.
CrossRef | PubMed
Inoue  T, Tomoike  H, Hisano  K, Nakamura  M; Endothelium determines flow-dependent dilation of the epicardial coronary in dogs. J Am Coll Cardiol. 11 1988:187-191.
CrossRef | PubMed
Sinoway  LI, Hendrickson  C, Davidson  WR  Jr, Prophet  S, Zelis  R; Characteristics of flow-mediated brachial artery vasodilation in human subjects. Circ Res. 64 1989:32-42.
CrossRef | PubMed
Nabel  EG, Selwyn  AP, Ganz  P; Large coronary arteries in humans are responsive to changing blood flow: an endothelium-dependent mechanism that fails in patients with atherosclerosis. J Am Coll Cardiol. 16 1990:349-356.
CrossRef | PubMed
Celermajer  DS, Sorensen  KE, Gooch  VM; Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet. 340 1992:1111-1115.
CrossRef | PubMed
[Pt 1]Celermajer  DS, Sorensen  KE, Georgakopoulos  D; Cigarette smoking is associated with dose-related and potentially reversible impairment of endothelium-dependent dilation in healthy young adults. Circulation. 88 1993:2149-2155.
CrossRef | PubMed
[abstract]Lieberman  EH, Uehata  A, Polak  J; Flow-mediated vasodilation is impaired in the brachial artery of patients with coronary artery disease or with diabetes mellitus. Clin Res. 41 1993:217A
Yeung  AC, Vekshtein  VI, Krantz  DS; The effect of atherosclerosis on the vasomotor response of coronary arteries to mental stress. N Engl J Med. 325 1991:1551-1556.
CrossRef | PubMed
[abstract]Uehata  A, Lieberman  EH, Meredith  IT, Anderson  TJ, Polak  J, Ganz  P, Selwyn  AP, Creager  M, Yeung  AC; Non-invasive assessment of flow-mediated vasodilation in brachial arteries: diminished response in young males compared to females. Circulation. 86 (Suppl I) 1992:I-620.
Liao  JK, Bettmann  MA, Sandor  T, Tucker  JI, Coleman  SM, Creager  MA; Differential impairment of vasodilator responsiveness of peripheral resistance and conduit vessels in humans with atherosclerosis. Circ Res. 68 1991:1027-1034.
CrossRef | PubMed
Creager  MA, Cooke  JP, Mendelsohn  ME; Impaired vasodilation of forearm resistance vessels in hypercholesterolemic humans. J Clin Invest. 86 1990:228-234.
CrossRef | PubMed
Panza  JA, Quyyumi  AA, Brush  JE  Jr, Epstein  SE; Abnormal endotheliumdependent vascular relaxation in patients with essential hypertension. N Engl J Med. 323 1990:22-27.
CrossRef | PubMed
Vallance  P, Collier  J, Moncada  S; Effects of endothelium-derived nitric oxide on peripheral arteriolar tone in man. Lancet. 2 1989:997-1000.
CrossRef | PubMed
Ohno  M, Gibbons  GH, Dzau  VJ, Cooke  JP; Shear stress elevates endothelial cGMP: role of a potassium channel and G protein coupling. Circulation. 88 1993:193-197.
CrossRef | PubMed
[abstract]Lieberman  EH, Knab  ST, Creager  MA; Nitric oxide mediates the vasodilator response to flow in humans. (Pt 2) Circulation. 90 1994:I-138.

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References

Moncada  S, Higgs  A; The l-arginine-nitric oxide pathway. N Engl J Med. 329 1993:2002-2012.
CrossRef | PubMed
Meredith  IT, Yeung  AC, Weidinger  FF; Role of impaired endotheliumdependent vasodilation in ischemic manifestations of coronary artery disease. Circulation. 87 (Suppl V) 1993:V
Ludmer  PL, Selwyn  AP, Shook  TL; Paradoxical vasoconstriction induced by acetylcholine in atherosclerosic coronary arteries. N Engl J Med. 315 1986:1046-1051.
CrossRef | PubMed
Zeiher  AM, Drexler  H, Wollschläger  H, Just  H; Modulation of coronary vasomotor tone in humans: progressive endothelial dysfunction with different stages of coronary atherosclerosis. Circulation. 83 1991:391-401.
CrossRef | PubMed
Yasue  H, Matsuyama  K, Okumura  K, Morikami  Y, Ogawa  H; Responses of angiographically normal human coronary arteries to intracoronary injection of acetylcholine by age and segment: possible role of early coronary atherosclerosis. Circulation. 81 1990:482-490.
CrossRef | PubMed
(Pt 2)Lefroy  DC, Crake  T, Uren  NG, Davies  GJ, Maseri  A; Effects of nitric oxide in the human coronary circulation. Circulation. 88 1993:I
CrossRef
Vita  JA, Treasure  CB, Nabel  EG; The coronary vasomotor response to acetylcholine relates to risk factors for coronary artery disease. Circulation. 81 1990:491-497.
CrossRef | PubMed
[abstract]Dyce  MC, Anderson  TJ, Orav  J; The relationship between endothelial vasodilator function and LDL particle size, density and number in human coronary atherosclerosis. (Pt 2) Circulation. 88 1993:1-466.
Leung  W-H, Lau  C-P, Wong  C-K; Beneficial effect of cholesterol-lowering on coronary endothelium-dependent relaxation in hypercholsterolaemic patients. Lancet. 341 1993:1496-1500.
CrossRef | PubMed
Poll  U, Holtz  J, Busse  R, Bassenge  E; Crucial role of endothelium in the vasodilator response to increased flow in vivo. Hypertension. 8 1986:37-44.
CrossRef | PubMed
Inoue  T, Tomoike  H, Hisano  K, Nakamura  M; Endothelium determines flow-dependent dilation of the epicardial coronary in dogs. J Am Coll Cardiol. 11 1988:187-191.
CrossRef | PubMed
Sinoway  LI, Hendrickson  C, Davidson  WR  Jr, Prophet  S, Zelis  R; Characteristics of flow-mediated brachial artery vasodilation in human subjects. Circ Res. 64 1989:32-42.
CrossRef | PubMed
Nabel  EG, Selwyn  AP, Ganz  P; Large coronary arteries in humans are responsive to changing blood flow: an endothelium-dependent mechanism that fails in patients with atherosclerosis. J Am Coll Cardiol. 16 1990:349-356.
CrossRef | PubMed
Celermajer  DS, Sorensen  KE, Gooch  VM; Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet. 340 1992:1111-1115.
CrossRef | PubMed
[Pt 1]Celermajer  DS, Sorensen  KE, Georgakopoulos  D; Cigarette smoking is associated with dose-related and potentially reversible impairment of endothelium-dependent dilation in healthy young adults. Circulation. 88 1993:2149-2155.
CrossRef | PubMed
[abstract]Lieberman  EH, Uehata  A, Polak  J; Flow-mediated vasodilation is impaired in the brachial artery of patients with coronary artery disease or with diabetes mellitus. Clin Res. 41 1993:217A
Yeung  AC, Vekshtein  VI, Krantz  DS; The effect of atherosclerosis on the vasomotor response of coronary arteries to mental stress. N Engl J Med. 325 1991:1551-1556.
CrossRef | PubMed
[abstract]Uehata  A, Lieberman  EH, Meredith  IT, Anderson  TJ, Polak  J, Ganz  P, Selwyn  AP, Creager  M, Yeung  AC; Non-invasive assessment of flow-mediated vasodilation in brachial arteries: diminished response in young males compared to females. Circulation. 86 (Suppl I) 1992:I-620.
Liao  JK, Bettmann  MA, Sandor  T, Tucker  JI, Coleman  SM, Creager  MA; Differential impairment of vasodilator responsiveness of peripheral resistance and conduit vessels in humans with atherosclerosis. Circ Res. 68 1991:1027-1034.
CrossRef | PubMed
Creager  MA, Cooke  JP, Mendelsohn  ME; Impaired vasodilation of forearm resistance vessels in hypercholesterolemic humans. J Clin Invest. 86 1990:228-234.
CrossRef | PubMed
Panza  JA, Quyyumi  AA, Brush  JE  Jr, Epstein  SE; Abnormal endotheliumdependent vascular relaxation in patients with essential hypertension. N Engl J Med. 323 1990:22-27.
CrossRef | PubMed
Vallance  P, Collier  J, Moncada  S; Effects of endothelium-derived nitric oxide on peripheral arteriolar tone in man. Lancet. 2 1989:997-1000.
CrossRef | PubMed
Ohno  M, Gibbons  GH, Dzau  VJ, Cooke  JP; Shear stress elevates endothelial cGMP: role of a potassium channel and G protein coupling. Circulation. 88 1993:193-197.
CrossRef | PubMed
[abstract]Lieberman  EH, Knab  ST, Creager  MA; Nitric oxide mediates the vasodilator response to flow in humans. (Pt 2) Circulation. 90 1994:I-138.

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