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Circulation, Vol 84, 1589-1596, Copyright © 1991 by American Heart Association
SH Kubo, TS Rector, AJ Bank, RE Williams and SM Heifetz
BACKGROUND. Endothelial cells produce a number of substances, collectively
termed endothelium-derived relaxing factor (EDRF), that promote local
relaxation of vascular smooth muscle. Although studies have demonstrated
defects in endothelium-dependent vasodilation in animal models of
hypertension, atherosclerosis, and heart failure, there are only limited
data from human subjects because of the difficulty in obtaining fresh
vascular segments. METHODS AND RESULTS. To address the hypothesis that
endothelium-dependent vasodilation is attenuated in patients with heart
failure, we measured forearm blood flow responses to the intra-arterial
administration of methacholine, a known stimulus of EDRF release through
muscarinic receptors. In 14 normal subjects, a dosage range of methacholine
increased forearm blood flow by 5.26 +/- 0.63, 10.50 +/- 0.63, and 13.22
+/- 0.86 ml/min/100 ml forearm volume (FAV); these responses were 1.98 +/-
0.46, 5.48 +/- 0.79, and 8.50 +/- 1.53 ml/min/100 ml FAV in 14 patients
with heart failure. When pooled over all doses, the responses were
strikingly less in the patients with heart failure (5.32 +/- 0.31 versus
9.52 +/- 0.60 ml/min/100 ml FAV; p = 0.0003). In a second study, the
average difference in forearm blood flow responses between patients with
heart failure and normal subjects with methacholine was significantly
greater than the average difference between the groups with nitroprusside
(4.04 +/- 1.10 versus 2.20 +/- 0.71 ml/min/100 ml FAV; p = 0.04). The
decreased methacholine responses in the patients with heart failure were
not related to age (r = 0.39; p = NS) or etiology because there was no
difference in the responses between patients with ischemic heart disease
and those with idiopathic cardiomyopathy. CONCLUSIONS. These data suggest
that endothelium-dependent vasodilation is attenuated in patients with
heart failure. Although the mechanisms of the decreased
endothelium-dependent responses in heart failure are not known, this
impaired local vasodilation may contribute to abnormalities in
vasoconstriction that are characteristic of heart failure.
ARTICLES
Endothelium-dependent vasodilation is attenuated in patients with heart failure
Cardiovascular Division, University of Minnesota, Minneapolis 55455.
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A. Bergdahl, S. Valdemarsson, M. Adner, X.-Y. Sun, T. Hedner, and L. Edvinsson Enhanced endothelin-1-induced contractions in mesenteric arteries from rats with congestive heart failure: role of ETB receptors Eur J Heart Fail, June 1, 2001; 3(3): 293 - 299. [Abstract] [Full Text] [PDF]
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S Adamopoulos, J Parissis, C Kroupis, M Georgiadis, D Karatzas, G Karavolias, K Koniavitou, A.J.S Coats, and D.T. Kremastinos Physical training reduces peripheral markers of inflammation in patients with chronic heart failure Eur. Heart J., May 1, 2001; 22(9): 791 - 797. [Abstract] [PDF]
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C. R. Gibbs, A. D. Blann, R. D. S. Watson, and G. Y. H. Lip Abnormalities of Hemorheological, Endothelial, and Platelet Function in Patients With Chronic Heart Failure in Sinus Rhythm : Effects of Angiotensin-Converting Enzyme Inhibitor and {beta}-Blocker Therapy Circulation, April 3, 2001; 103(13): 1746 - 1751. [Abstract] [Full Text] [PDF]
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A. K. Nightingale, D. J. Blackman, G. R. Ellis, M. Schmitt, J. A. Morris-Thurgood, E. A. Jones, and M. P. Frenneaux Preservation of venous endothelial function in the forearm venous capacitance bed of patients with chronic heart failure despite arterial endothelial dysfunction J. Am. Coll. Cardiol., March 15, 2001; 37(4): 1062 - 1068. [Abstract] [Full Text] [PDF]
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A. Linke, N. Schoene, S. Gielen, J.u. Hofer, S. Erbs, G. Schuler, and R. Hambrecht Endothelial dysfunction in patients with chronic heart failure: systemic effects of lower-limb exercise training J. Am. Coll. Cardiol., February 1, 2001; 37(2): 392 - 397. [Abstract] [Full Text] [PDF]
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T. Hisaoka, M. Yano, T. Ohkusa, M. Suetsugu, K. Ono, M. Kohno, J. Yamada, S. Kobayashi, M. Kohno, and M. Matsuzaki Enhancement of Rho/Rho-kinase system in regulation of vascular smooth muscle contraction in tachycardia-induced heart failure Cardiovasc Res, February 1, 2001; 49(2): 319 - 329. [Abstract] [Full Text] [PDF]
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A. R. Patel, J. T. Kuvin, N. G. Pandian, J. J. Smith, J. E. Udelson, M. E. Mendelsohn, M. A. Konstam, and R. H. Karas Heart failure etiology affects peripheral vascular endothelial function after cardiac transplantation J. Am. Coll. Cardiol., January 1, 2001; 37(1): 195 - 200. [Abstract] [Full Text] [PDF]
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J.-N. Trochu, J.-B. Bouhour, G. Kaley, and T. H. Hintze Role of Endothelium-Derived Nitric Oxide in the Regulation of Cardiac Oxygen Metabolism : Implications in Health and Disease Circ. Res., December 8, 2000; 87(12): 1108 - 1117. [Abstract] [Full Text] [PDF]
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L. Rossig, J. Haendeler, Z. Mallat, B. Hugel, J.-M. Freyssinet, A. Tedgui, S. Dimmeler, and A. M. Zeiher Congestive heart failure induces endothelial cell apoptosis: protective role of carvedilol J. Am. Coll. Cardiol., December 1, 2000; 36(7): 2081 - 2089. [Abstract] [Full Text] [PDF]
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D. M. Kaye, B. A. Ahlers, D. J. Autelitano, and J. P. F. Chin-Dusting In Vivo and In Vitro Evidence for Impaired Arginine Transport in Human Heart Failure Circulation, November 28, 2000; 102(22): 2707 - 2712. [Abstract] [Full Text] [PDF]
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M. Kato, P. Roberts-Thomson, B. G. Phillips, W. G. Haynes, M. Winnicki, V. Accurso, and V. K. Somers Impairment of Endothelium-Dependent Vasodilation of Resistance Vessels in Patients With Obstructive Sleep Apnea Circulation, November 21, 2000; 102(21): 2607 - 2610. [Abstract] [Full Text] [PDF]
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Y. Ishibashi, T. Shimada, T. Sakane, N. Takahashi, T. Sugamori, S. Ohhata, S.-i. Inoue, H. Katoh, K. Sano, Y. Murakami, et al. Contribution of endogenous nitric oxide to basal vasomotor tone of peripheral vessels and plasma B-Type natriuretic peptide levels in patients with congestive heart failure J. Am. Coll. Cardiol., November 1, 2000; 36(5): 1605 - 1611. [Abstract] [Full Text] [PDF]
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K. Sakata, R. Nawada, K. Ohbayashi, H. Tamekiyo, and H. Yoshida Diffuse and Severe Left Ventricular Dysfunction Induced by Epicardial Coronary Artery Spasm Angiology, October 1, 2000; 51(10): 837 - 847. [Abstract] [PDF]
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A. Maiorana, G. O'Driscoll, L. Dembo, C. Cheetham, C. Goodman, R. Taylor, and D. Green Effect of aerobic and resistance exercise training on vascular function in heart failure Am J Physiol Heart Circ Physiol, October 1, 2000; 279(4): H1999 - H2005. [Abstract] [Full Text] [PDF]
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S. D. Katz, K. Balidemaj, S. Homma, H. Wu, J. Wang, and S. Maybaum Acute type 5 phosphodiesterase inhibition with sildenafil enhances flow-mediated vasodilation in patients with chronic heart failure J. Am. Coll. Cardiol., September 1, 2000; 36(3): 845 - 851. [Abstract] [Full Text] [PDF]
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R. Varin, P. Mulder, F. Tamion, V. Richard, J.-P. Henry, F. Lallemand, G. Lerebours, and C. Thuillez Improvement of Endothelial Function by Chronic Angiotensin-Converting Enzyme Inhibition in Heart Failure : Role of Nitric Oxide, Prostanoids, Oxidant Stress, and Bradykinin Circulation, July 18, 2000; 102(3): 351 - 356. [Abstract] [Full Text] [PDF]
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J. Bauersachs, D. Fraccarollo, P. Galuppo, J. Widder, and G. Ertl Endothelin-receptor blockade improves endothelial vasomotor dysfunction in heart failure Cardiovasc Res, July 1, 2000; 47(1): 142 - 149. [Abstract] [Full Text] [PDF]
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C. Berry, C. A. Hamilton, M. J. Brosnan, F. G. Magill, G. A. Berg, J. J. V. McMurray, and A. F. Dominiczak Investigation Into the Sources of Superoxide in Human Blood Vessels : Angiotensin II Increases Superoxide Production in Human Internal Mammary Arteries Circulation, May 9, 2000; 101(18): 2206 - 2212. [Abstract] [Full Text] [PDF]
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R. Hambrecht, L. Hilbrich, S. Erbs, S. Gielen, E. Fiehn, N. Schoene, and G. Schuler Correction of endothelial dysfunction in chronic heart failure: additional effects of exercise training and oral L-arginine supplementation J. Am. Coll. Cardiol., March 1, 2000; 35(3): 706 - 713. [Abstract] [Full Text] [PDF]
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R. Levi, R. Maruyama, N. C. E. Smith, and N. Seyedi Is the lower mortality in patients treated with aspirin and angiotensin-converting enzyme inhibitors due to decreased norepinephrine release? J. Am. Coll. Cardiol., March 1, 2000; 35(3): 817 - 818. [Full Text] [PDF]
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K. Kiilavuori, H. Naveri, T. Salmi, and M. Harkonen The effect of physical training on skeletal muscle in patients with chronic heart failure Eur J Heart Fail, March 1, 2000; 2(1): 53 - 63. [Abstract] [Full Text] [PDF]
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D. Sun, A. Huang, G. Zhao, R. Bernstein, P. Forfia, X. Xu, A. Koller, G. Kaley, and T. H. Hintze Reduced NO-dependent arteriolar dilation during the development of cardiomyopathy Am J Physiol Heart Circ Physiol, February 1, 2000; 278(2): H461 - H468. [Abstract] [Full Text] [PDF]
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C. E. Negrao, M. A. Hamilton, G. C. Fonarow, A. Hage, J. D. Moriguchi, and H. R. Middlekauff Impaired endothelium-mediated vasodilation is not the principal cause of vasoconstriction in heart failure Am J Physiol Heart Circ Physiol, January 1, 2000; 278(1): H168 - H174. [Abstract] [Full Text] [PDF]
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D. P. Thomas and O. Hudlicka Arteriolar reactivity and capillarization in chronically stimulated rat limb skeletal muscle post-MI J Appl Physiol, December 1, 1999; 87(6): 2259 - 2265. [Abstract] [Full Text] [PDF]
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L. Comini, T. Bachetti, L. Agnoletti, G. Gaia, S. Curello, B. Milanesi, M. Volterrani, G. Parrinello, C. Ceconi, A. Giordano, et al. Induction of functional inducible nitric oxide synthase in monocytes of patients with congestive heart failure. Link with tumour necrosis factor-{alpha} Eur. Heart J., October 2, 1999; 20(20): 1503 - 1513. [Abstract] [PDF]
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