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Circulation, Vol 89, 1580-1586, Copyright © 1994 by American Heart Association
CM Wei, A Lerman, RJ Rodeheffer, CG McGregor, RR Brandt, S Wright, DM Heublein, PC Kao, WD Edwards and JC Burnett Jr
BACKGROUND: Although recent investigations report the elevation of plasma
endothelin (ET) in congestive heart failure (CHF), it remains unclear if
this elevation is that of the biologically active peptide ET- 1 or of its
precursor big-ET. Furthermore, it is unclear if such elevation is
associated with increased myocardial ET and if the molecular form from
cardiac tissue is altered ET. Last, it remains to be established whether
circulating ET is increased at the earliest stage of CHF in patients with
asymptomatic left ventricular dysfunction and correlates with the magnitude
of ventricular dysfunction. METHODS AND RESULTS: The present study was
designed to investigate concentrations and molecular forms of ET in plasma
and cardiac tissue in healthy subjects and CHF patients with New York Heart
Association (NYHA) class I through IV using cardiac radionuclide angiogram,
cardiac myocardial biopsy, radioimmunoassay, gel permeation chromatography
(GPC), and immunohistochemical staining (IHCS). Plasma ET was increased
only in patients with moderate (NYHA class III) or severe (NYHA class IV)
CHF compared with healthy subjects and individuals with asymptomatic (NYHA
class I) or mild (NYHA class II) CHF. The elevation of circulating ET in
CHF showed a negative correlation with left ventricular ejection fraction
and cardiac index and a positive correlation with functional class and left
ventricular end-diastolic volume index. GPC demonstrated that
immunoreactive plasma ET was ET-1 in healthy subjects and both mature ET-1
and its precursor big-ET in severe CHF patients, with big-ET the
predominant molecular form. Cardiac tissue concentrations and IHCS revealed
ET presence in healthy atrial and ventricular tissue, which were not
different in severe CHF. GPC revealed that the molecular form of cardiac ET
was ET-1 in both healthy and CHF hearts. CONCLUSIONS: The present study
establishes for the first time that the elevation of plasma ET in severe
human CHF represents principally elevation of big-ET. Second, ET is present
in healthy and failing myocardia, and its activity by both
immunohistochemistry and radioimmunoassay is not changed in CHF.
Furthermore, the elevated plasma ET is characteristic of severe CHF and not
asymptomatic or mild CHF. In addition, the degree of plasma elevation of ET
correlates with the magnitude of alterations in cardiac hemodynamics and
functional class. The present study confirms and extends previous
investigations of ET in human CHF and establishes the evolution of
circulating and local cardiac ET in the spectrum of human CHF.
ARTICLES
Endothelin in human congestive heart failure
Cardiorenal Research Laboratory, Mayo Clinic and Foundation, Rochester, MN 55905.
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H. Kjekshus, O. A. Smiseth, R. Klinge, E. Oie, M. E. Hystad, and H. Attramadal Regulation of ET: pulmonary release of ET contributes to increased plasma ET levels and vasoconstriction in CHF Am J Physiol Heart Circ Physiol, April 1, 2000; 278(4): H1299 - H1310. [Abstract] [Full Text] [PDF]
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G. G. N. Serneri, I. Cecioni, S. Vanni, R. Paniccia, B. Bandinelli, A. Vetere, X. Janming, I. Bertolozzi, M. Boddi, G. F. Lisi, et al. Selective Upregulation of Cardiac Endothelin System in Patients With Ischemic but Not Idiopathic Dilated Cardiomyopathy : Endothelin-1 System in the Human Failing Heart Circ. Res., March 3, 2000; 86(4): 377 - 385. [Abstract] [Full Text] [PDF]
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M. T. Rademaker, V. A. Cameron, C. J. Charles, E. A. Espiner, M. G. Nicholls, C. J. Pemberton, and A. M. Richards Neurohormones in an ovine model of compensated postinfarction left ventricular dysfunction Am J Physiol Heart Circ Physiol, March 1, 2000; 278(3): H731 - H740. [Abstract] [Full Text] [PDF]
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P. A. MacCarthy, R. Grocott-Mason, B. D. Prendergast, and A. M. Shah Contrasting Inotropic Effects of Endogenous Endothelin in the Normal and Failing Human Heart : Studies With an Intracoronary ETA Receptor Antagonist Circulation, January 18, 2000; 101(2): 142 - 147. [Abstract] [Full Text] [PDF]
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T. Mishima, M. Tanimura, G. Suzuki, A. Todor, V. G. Sharov, S. Goldstein, and H. N. Sabbah Effects of long-term therapy with bosentan on the progression of left ventricular dysfunction and remodeling in dogs with heart failure J. Am. Coll. Cardiol., January 1, 2000; 35(1): 222 - 229. [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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C. Wei and J. C. Burnett Jr. Inhibition by calcium antagonism of circulating and renal endothelin in experimental congestive heart failure Am J Physiol Heart Circ Physiol, January 1, 2000; 278(1): H263 - H268. [Abstract] [Full Text] [PDF]
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K. Ono, A. Matsumori, T. Shioi, Y. Furukawa, and S. Sasayama Contribution of Endothelin-1 to Myocardial Injury in a Murine Model of Myocarditis : Acute Effects of Bosentan, an Endothelin Receptor Antagonist Circulation, October 26, 1999; 100(17): 1823 - 1829. [Abstract] [Full Text] [PDF]
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 R. Bajoria, M. Sullivan, and N. M. Fisk Endothelin concentrations in monochorionic twins with severe twin–twin transfusion syndrome Hum. Reprod., June 1, 1999; 14(6): 1614 - 1618. [Abstract] [Full Text] [PDF]
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L. Tiret, O. Poirier, V. Hallet, T. A. McDonagh, C. Morrison, J. J. V. McMurray, H. J. Dargie, D. Arveiler, J.-B. Ruidavets, G. Luc, et al. The Lys198Asn Polymorphism in the Endothelin-1 Gene Is Associated With Blood Pressure in Overweight People Hypertension, May 1, 1999; 33(5): 1169 - 1174. [Abstract] [Full Text] [PDF]
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O. Zolk, J. Quattek, G. Sitzler, T. Schrader, G. Nickenig, P. Schnabel, K. Shimada, M. Takahashi, and M. Bohm Expression of Endothelin-1, Endothelin-Converting Enzyme, and Endothelin Receptors in Chronic Heart Failure Circulation, April 27, 1999; 99(16): 2118 - 2123. [Abstract] [Full Text] [PDF]
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B. Pieske, B. Beyermann, V. Breu, B. M. Loffler, K. Schlotthauer, L. S. Maier, S. Schmidt-Schweda, H. Just, and G. Hasenfuss Functional Effects of Endothelin and Regulation of Endothelin Receptors in Isolated Human Nonfailing and Failing Myocardium Circulation, April 13, 1999; 99(14): 1802 - 1809. [Abstract] [Full Text] [PDF]
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J. D. Parker, J. J. Thiessen, R. Reilly, J. H. Tong, D. J. Stewart, and A. S. Pandey Human Endothelin-1 Clearance Kinetics Revealed by a Radiotracer Technique J. Pharmacol. Exp. Ther., April 1, 1999; 289(1): 261 - 265. [Abstract] [Full Text]
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P. J. Cowburn, J. G. F. Cleland, J. D. McArthur, M. R. MacLean, J. J. V. McMurray, H. J. Dargie, and J. J. Morton EndothelinB receptors are functionally important in mediating vasoconstriction in the systemic circulation in patients with left ventricular systolic dysfunction J. Am. Coll. Cardiol., March 15, 1999; 33(4): 932 - 938. [Abstract] [Full Text] [PDF]
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K. Onishi, M. Ohno, W. C. Little, and C.-P. Cheng Endogenous Endothelin-1 Depresses Left Ventricular Systolic and Diastolic Performance in Congestive Heart Failure J. Pharmacol. Exp. Ther., March 1, 1999; 288(3): 1214 - 1222. [Abstract] [Full Text]
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T. Inada, H. Fujiwara, K. Hasegawa, M. Araki, R. Yamauchi-Kohno, H. Yabana, T. Fujiwara, M. Tanaka, and S. Sasayama Upregulated expression of cardiac endothelin-1 participates in myocardial cell growth in Bio14.6 Syrian cardiomyopathic hamsters J. Am. Coll. Cardiol., February 1, 1999; 33(2): 565 - 571. [Abstract] [Full Text] [PDF]
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S. Kaburagi, K. Hasegawa, T. Morimoto, M. Araki, T. Sawamura, T. Masaki, and S. Sasayama The Role of Endothelin-Converting Enzyme-1 in the Development of {alpha}1-Adrenergic-Stimulated Hypertrophy in Cultured Neonatal Rat Cardiac Myocytes Circulation, January 19, 1999; 99(2): 292 - 298. [Abstract] [Full Text] [PDF]
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 I. Anwaar, A. Gottsater, F. Lindgarde, and I. Mattiasson Increasing Plasma Neopterin and Persistent Plasma Endothelin During Follow-up After Acute Cerebral Ischemia Angiology, January 1, 1999; 50(1): 1 - 8. [Abstract] [PDF]
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G. Sutsch, W. Kiowski, X.-W. Yan, P. Hunziker, S. Christen, W. Strobel, J.-H. Kim, P. Rickenbacher, and O. Bertel Short-Term Oral Endothelin-Receptor Antagonist Therapy in Conventionally Treated Patients With Symptomatic Severe Chronic Heart Failure Circulation, November 24, 1998; 98(21): 2262 - 2268. [Abstract] [Full Text] [PDF]
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M. Hulsmann, B. Stanek, B. Frey, B. Sturm, D. Putz, T. Kos, R. Berger, W. Woloszczuk, G. Maurer, and R. Pacher Value of cardiopulmonary exercise testing and big endothelin plasma levels to predict short-term prognosis of patients with chronic heart failure J. Am. Coll. Cardiol., November 15, 1998; 32(6): 1695 - 1700. [Abstract] [Full Text] [PDF]
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K. Alexiou, T. Dschietzig, O. Simsch, M. Laule, J. Hundertmark, G. Baumann, and K. Stangl Arrhythmogenic effects induced by coronary conversion of pulmonary big endothelin to endothelin: Aggravation of this phenomenon in heritable hyperlipidemia J. Am. Coll. Cardiol., November 15, 1998; 32(6): 1773 - 1778. [Abstract] [Full Text] [PDF]
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D. Saad, R. Mukherjee, P. B. Thomas, J. P. Iannini, C. G. Basler, L. Hebbar, S.-J. O, S. Moreland, M. L. Webb, J. R. Powell, et al. The effects of endothelin-A receptor blockade during the progression of pacing-induced congestive heart failure J. Am. Coll. Cardiol., November 15, 1998; 32(6): 1779 - 1786. [Abstract] [Full Text] [PDF]
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Y. Iwanaga, Y. Kihara, K. Hasegawa, K. Inagaki, T. Yoneda, S. Kaburagi, M. Araki, and S. Sasayama Cardiac Endothelin-1 Plays a Critical Role in the Functional Deterioration of Left Ventricles During the Transition From Compensatory Hypertrophy to Congestive Heart Failure in Salt-Sensitive Hypertensive Rats Circulation, November 10, 1998; 98(19): 2065 - 2073. [Abstract] [Full Text] [PDF]
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F. G. Spinale, R. Mukherjee, R. S. Krombach, M. J. Clair, J. W. Hendrick, W. V. Houck, L. Hebbar, S. B. Kribbs, J. L. Zellner, and M. G. Dodd Chronic Amlodipine Treatment During the Development of Heart Failure Circulation, October 20, 1998; 98(16): 1666 - 1674. [Abstract] [Full Text] [PDF]
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J. Dupuis, J.-L. Rouleau, and P. Cernacek Reduced Pulmonary Clearance of Endothelin-1 Contributes to the Increase of Circulating Levels in Heart Failure Secondary to Myocardial Infarction Circulation, October 20, 1998; 98(16): 1684 - 1687. [Abstract] [Full Text] [PDF]
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 B. W. Mays, T. Ripple, M. T. Eginton, G. R. Seabrook, R. A. Cambria, J. B. Towne, and J. A. Freischlag Smoking Cessation Reverses Arterial Endothelium-Dependent Relaxation Injury Vascular and Endovascular Surgery, September 1, 1998; 32(5): 407 - 413. [Abstract] [PDF]
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P. J. Cowburn, J. G.F. Cleland, J. D. McArthur, M. R. MacLean, H. J. Dargie, J. J.V. McMurray, and J. J. Morton Endothelin-1 has haemodynamic effects at pathophysiological concentrations in patients with left ventricular dysfunction Cardiovasc Res, September 1, 1998; 39(3): 563 - 570. [Abstract] [Full Text] [PDF]
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G. W Moe, A. Albernaz, G. O Naik, M. Kirchengast, and D. J Stewart Beneficial effects of long-term selective endothelin type A receptor blockade in canine experimental heart failure Cardiovasc Res, September 1, 1998; 39(3): 571 - 579. [Abstract] [Full Text] [PDF]
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R. Choussat, L. Hittinger, F. Barbe, G. Maistre, A. Carayon, B. Crozatier, and J. Su Acute effects of an endothelin-1 receptor antagonist bosentan at different stages of heart failure in conscious dogs Cardiovasc Res, September 1, 1998; 39(3): 580 - 588. [Abstract] [Full Text] [PDF]
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M. Suzuki, N. Ohte, Z.-M. Wang, D. L. Williams Jr., W. C. Little, and C.-P. Cheng Altered inotropic response of endothelin-1 in cardiomyocytes from rats with isoproterenol-induced cardiomyopathy Cardiovasc Res, September 1, 1998; 39(3): 589 - 599. [Abstract] [Full Text] [PDF]
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P. Mulder, V. Richard, F. Bouchart, G. Derumeaux, K. Munter, and C. Thuillez Selective ETA receptor blockade prevents left ventricular remodeling and deterioration of cardiac function in experimental heart failure Cardiovasc Res, September 1, 1998; 39(3): 600 - 608. [Abstract] [Full Text] [PDF]
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S M Maguire, A G Nugent, C McGurk, G D Johnston, and D P Nicholls Abnormal vascular responses in human chronic cardiac failure are both endothelium dependent and endothelium independent Heart, August 1, 1998; 80(2): 141 - 145. [Abstract] [Full Text]
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R.S. Krombach, M. J Clair, J. W Hendrick, W. V Houck, J. L Zellner, S. B Kribbs, S. Whitebread, R. Mukherjee, M. de Gasparo, and F. G Spinale Angiotensin converting enzyme inhibition, AT1 receptor inhibition, and combination therapy with pacing induced heart failure: effects on left ventricular performance and regional blood flow patterns Cardiovasc Res, June 1, 1998; 38(3): 631 - 645. [Abstract] [Full Text] [PDF]
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B. Bozkurt, S. B. Kribbs, F. J. Clubb Jr, L. H. Michael, V. V. Didenko, P. J. Hornsby, Y. Seta, H. Oral, F. G. Spinale, and D. L. Mann Pathophysiologically Relevant Concentrations of Tumor Necrosis Factor-{alpha} Promote Progressive Left Ventricular Dysfunction and Remodeling in Rats Circulation, April 14, 1998; 97(14): 1382 - 1391. [Abstract] [Full Text] [PDF]
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