Circulation, Vol 85, 504-509, Copyright © 1992 by American Heart Association
RJ Cody, GJ Haas, PF Binkley, Q Capers and R Kelley
BACKGROUND. Endothelin is a family of potent vasoconstrictor peptides of
vascular endothelial origin. Although it has been proposed that the
vasoconstrictor effects of endothelin are produced at the local vascular
level, increased plasma concentration of endothelin has been identified in
cardiovascular disorders. METHODS AND RESULTS. We tested whether
immunoreactive endothelin-1 could be detected by radioimmunoassay in plasma
of congestive heart failure patients and whether levels correlated with
hemodynamic characteristics. Twenty congestive heart failure patients (New
York Heart Association class II- IV) were sampled in the morning after an
overnight fast, before medication. Cardiac index was decreased to 2.14 +/-
0.45 l/m/m2, and pulmonary wedge pressure was increased to 22 +/- 7 mm Hg.
The ranges of pulmonary pressures were: systolic, 22-100 mm Hg, mean, 13-61
mm Hg, and diastolic, 8-42 mm Hg. The endothelin-1 level was 9.07 +/- 4.13
pg/ml (range, 4-19 pg/ml), which was increased compared with 12 normals
(3.7 +/- 0.6 pg/ml; range, 2.8-4.7 pg/ml); the difference was statistically
significant (p less than 0.0001). Endothelin-1 significantly correlated
with pulmonary pressures (systolic, r = 0.78; mean, r = 0.80; diastolic, r
= 0.77; all p less than 0.003) and pulmonary vascular resistance (r = 0.65,
p less than 0.01). Endothelin- 1 strongly correlated with the resistance
ratio (pulmonary vascular resistance/systemic vascular resistance) (r =
0.88, p less than 0.0001). Stepwise multiple regression analysis confirmed
the significance of these observations. CONCLUSIONS. Elevated
immunoreactive endothelin-1 specifically correlated with the extent of
pulmonary hypertension in congestive heart failure patients. Whether
endothelin-1 is a regional mediator of pulmonary hypertension or a marker
for its occurrence requires additional evaluation.
ARTICLES
Plasma endothelin correlates with the extent of pulmonary hypertension in patients with chronic congestive heart failure [published erratum appears in Circulation 1993 Mar;87(3):1064]
Department of Medicine, Ohio State University Hospitals, College of Medicine, Columbus, Ohio 43210.
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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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M Mundhenke, B Schwartzkopff, M Köstering, U Deska, R M Klein, and B E Strauer Endogenous plasma endothelin concentrations and coronary circulation in patients with mild dilated cardiomyopathy Heart, March 1, 1999; 81(3): 278 - 284. [Abstract] [Full Text]
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T. Tsutamoto, A. Wada, T. Hisanaga, K. Maeda, M. Ohnishi, N. Mabuchi, M. Sawaki, M. Hayashi, M. Fujii, and M. Kinoshita Relationship between endothelin-1 extraction in the peripheral circulation and systemic vascular resistance in patients with severe congestive heart failure J. Am. Coll. Cardiol., February 1, 1999; 33(2): 530 - 537. [Abstract] [Full Text] [PDF]
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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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Y. KAGAYA, H. OTANI, T. TANIKAWA, S. NAMIUCHI, S. ISOYAMA, and K. SHIRATO Concentrations of angiotensin II, endothelin-1, and BNP in the coronary sinus and ascending aorta of patients with heart disease Heart, January 1, 1999; 81(1): 102 - 103. [Full Text]
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F. E. Strachan, J. C. Spratt, I. B. Wilkinson, N. R. Johnston, G. A. Gray, and D. J. Webb Systemic Blockade of the Endothelin-B Receptor Increases Peripheral Vascular Resistance in Healthy Men Hypertension, January 1, 1999; 33(1): 581 - 585. [Abstract] [Full Text] [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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Q. T. Nguyen, P. Cernacek, A. Calderoni, D. J. Stewart, P. Picard, P. Sirois, M. White, and J. L. Rouleau Endothelin A Receptor Blockade Causes Adverse Left Ventricular Remodeling but Improves Pulmonary Artery Pressure After Infarction in the Rat Circulation, November 24, 1998; 98(21): 2323 - 2330. [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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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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E. Oie, R. Bjonerheim, H. K. Grogaard, H. Kongshaug, O. A. Smiseth, and H. Attramadal ET-receptor antagonism, myocardial gene expression, and ventricular remodeling during CHF in rats Am J Physiol Heart Circ Physiol, September 1, 1998; 275(3): H868 - H877. [Abstract] [Full Text] [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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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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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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J. Dupuis, G. W Moe, and P. Cernacek Reduced pulmonary metabolism of endothelin-1 in canine tachycardia-induced heart failure Cardiovasc Res, September 1, 1998; 39(3): 609 - 616. [Abstract] [Full Text] [PDF]
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M. Ohnishi, A. Wada, T. Tsutamoto, D. Fukai, and M. Kinoshita Comparison of the acute effects of a selective endothelin ETA and a mixed ETA/ETB receptor antagonist in heart failure Cardiovasc Res, September 1, 1998; 39(3): 617 - 624. [Abstract] [Full Text] [PDF]
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D E Newby, N E R Goodfield, A D Flapan, N A Boon, K A A Fox, and D J Webb Regulation of peripheral vascular tone in patients with heart failure: contribution of angiotensin II Heart, August 1, 1998; 80(2): 134 - 140. [Abstract] [Full Text]
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C. J. Ferro, J. C. Spratt, W. G. Haynes, and D. J. Webb Inhibition of Neutral Endopeptidase Causes Vasoconstriction of Human Resistance Vessels In Vivo Circulation, June 16, 1998; 97(23): 2323 - 2330. [Abstract] [Full Text] [PDF]
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S. Prie, D. J. Stewart, and J. Dupuis EndothelinA Receptor Blockade Improves Nitric Oxide–Mediated Vasodilation in Monocrotaline-Induced Pulmonary Hypertension Circulation, June 2, 1998; 97(21): 2169 - 2174. [Abstract] [Full Text] [PDF]
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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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G. A Deuchar, M. N Hicks, S. M Cobbe, C. C Docherty, and M. R MacLean Pulmonary responses to 5-hydroxytryptamine and endothelin-1 in a rabbit model of left ventricular dysfunction Cardiovasc Res, May 1, 1998; 38(2): 500 - 507. [Abstract] [Full Text] [PDF]
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D. E. Newby, R. Jalan, S. Masumori, P. C. Hayes, N. A. Boon, and D. J. Webb Peripheral vascular tone in patients with cirrhosis: role of the renin-angiotensin and sympathetic nervous systems Cardiovasc Res, April 1, 1998; 38(1): 221 - 228. [Abstract] [Full Text] [PDF]
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 C. C. Docherty and M. R. Maclean EndothelinB Receptors in Rabbit Pulmonary Resistance Arteries: Effect of Left Ventricular Dysfunction J. Pharmacol. Exp. Ther., March 1, 1998; 284(3): 895 - 903. [Abstract] [Full Text]
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D. D. Borgeson, J. A. Grantham, E. E. Williamson, A. Luchner, M. M. Redfield, T. J. Opgenorth, and J. C. Burnett Jr Chronic Oral Endothelin Type A Receptor Antagonism in Experimental Heart Failure Hypertension, March 1, 1998; 31(3): 766 - 770. [Abstract] [Full Text] [PDF]
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C. Haug, W. Koenig, M. Hoeher, M. Kochs, V. Hombach, A. Gruenert, and H. Osterhues Direct enzyme immunometric measurement of plasma big endothelin-1 concentrations and correlation with indicators of left ventricular function Clin. Chem., February 1, 1998; 44(2): 239 - 243. [Abstract] [Full Text] [PDF]
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D. C. Underwood, S. Bochnowicz, R. R. Osborn, M. A. Luttmann, and D. W. P. Hay Nonpeptide Endothelin Receptor Antagonists. X. Inhibition of Endothelin-1- and Hypoxia-Induced Pulmonary Pressor Responses in the Guinea Pig by the Endothelin Receptor Antagonist, SB 217242 J. Pharmacol. Exp. Ther., December 1, 1997; 283(3): 1130 - 1137. [Abstract] [Full Text]
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K. Graf, Y. S. Do, N. Ashizawa, W. P. Meehan, C. M. Giachelli, C. C. Marboe, E. Fleck, and W. A. Hsueh Myocardial Osteopontin Expression Is Associated With Left Ventricular Hypertrophy Circulation, November 4, 1997; 96(9): 3063 - 3071. [Abstract] [Full Text]
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F. G. Spinale, M. de Gasparo, S. Whitebread, L. Hebbar, M. J. Clair, D. M. Melton, R. S. Krombach, R. Mukherjee, J. P. Iannini, and S.-J. O Modulation of the Renin-Angiotensin Pathway Through Enzyme Inhibition and Specific Receptor Blockade in Pacing-Induced Heart Failure : I. Effects on Left Ventricular Performance and Neurohormonal Systems Circulation, October 7, 1997; 96(7): 2385 - 2396. [Abstract] [Full Text]
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