Plasma endothelin concentrations in humans with end-stage heart failure and after heart transplantation

Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, Minnesota 55905.

OBJECTIVES AND BACKGROUND. Endothelin is an endothelium-derived vasoconstrictor peptide that increases systemic and renal vascular resistance at pathophysiologic concentrations. Recent studies have demonstrated its presence in the circulation and its elevation in animals with congestive heart failure, suggesting that endothelin may contribute to the vasoconstrictive state of heart failure. The current study was designed with two objectives: 1) to demonstrate the elevation of circulating endothelin in patients with heart failure, and 2) to determine the short- and long-term response of endothelin levels after heart transplantation. METHODS. Plasma endothelin concentrations were measured in two patient groups. Group 1 included 24 patients with end-stage heart failure who were studied during evaluation for potential heart transplantation. Group 2 included 12 patients from Group 1 who had had heart transplantation. Plasma endothelin concentrations were measured before and on days 1, 3 and 7 after heart transplantation. Eight of these patients also had levels measured 3 to 12 months later. RESULTS. Plasma endothelin concentrations were significantly elevated in patients with heart failure compared with those in an age-matched control group (11.7 +/- 1.1 vs. 6.8 +/- 0.3 pg/ml). In response to heart transplantation, plasma endothelin concentrations increased further and were sustained during a long-term follow-up. These later changes were associated with a significant increase in arterial pressure and serum creatinine. CONCLUSIONS. This study demonstrates that endothelin concentrations are increased in patients with heart failure and increase further after heart transplantation. It suggests a possible role for endothelin in the cardiovascular and renal adaptive responses to human heart transplantation.

This article has been cited by other articles:

				M. Gujic, A. Houssiere, O. Xhaet, J.-F. Argacha, N. Denewet, A. Noseda, P. Jespers, C. Melot, R. Naeije, and P. van de Borne Does Endothelin Play a Role in Chemoreception During Acute Hypoxia in Normal Men? Chest, May 1, 2007; 131(5): 1467 - 1472. [Abstract] [Full Text] [PDF]

				D. Konrad, A. Oldner, M. Wanecek, A. Rudehill, E. Weitzberg, B. Biber, G. Johansson, S. Haggmark, and M. Haney Positive inotropic and negative lusitropic effects of endothelin receptor agonism in vivo Am J Physiol Heart Circ Physiol, October 1, 2005; 289(4): H1702 - H1709. [Abstract] [Full Text] [PDF]

				T. G von Lueder, H. Kjekshus, T. Edvardsen, E. Oie, S. Urheim, L. E. Vinge, M. S. Ahmed, O. A Smiseth, and H. Attramadal Mechanisms of elevated plasma endothelin-1 in CHF: congestion increases pulmonary synthesis and secretion of endothelin-1 Cardiovasc Res, July 1, 2004; 63(1): 41 - 50. [Abstract] [Full Text] [PDF]

				J. D. Parker and J. J. Thiessen Increased endothelin-1 production in patients with chronic heart failure Am J Physiol Heart Circ Physiol, March 1, 2004; 286(3): H1141 - H1145. [Abstract] [Full Text] [PDF]

				P.J. Cowburn and J.G.F. Cleland Endothelin antagonists for chronic heart failure: do they have a role? Eur. Heart J., October 1, 2001; 22(19): 1772 - 1784. [PDF]

				B. Geny, R. Richard, B. Mettauer, J. Lonsdorfer, and F. Piquard Cardiac natriuretic peptides during exercise and training after heart transplantation Cardiovasc Res, August 15, 2001; 51(3): 521 - 528. [Full Text] [PDF]

				L. E. Spieker, G. Noll, F. T. Ruschitzka, and T. F. Luscher Endothelin receptor antagonists in congestive heart failure: a new therapeutic principle for the future? J. Am. Coll. Cardiol., May 1, 2001; 37(6): 1493 - 1505. [Abstract] [Full Text] [PDF]

				T. Suzuki and T. Miyauchi A novel pharmacological action of ET-1 to prevent the cytotoxicity of doxorubicin in cardiomyocytes Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2001; 280(5): R1399 - R1406. [Abstract] [Full Text] [PDF]

				A. Luchner, M. Jougasaki, E. Friedrich, D. D. Borgeson, T. L. Stevens, M. M. Redfield, G. A. J. Riegger, and J. C. Burnett Jr. Activation of cardiorenal and pulmonary tissue endothelin-1 in experimental heart failure Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2000; 279(3): R974 - R979. [Abstract] [Full Text] [PDF]

				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]

				R. G. Masters, R. A. Davies, J. P. Veinot, P. J. Hendry, S. J. Smith, and A. J. de Bold Discoordinate Modulation of Natriuretic Peptides During Acute Cardiac Allograft Rejection in Humans Circulation, July 20, 1999; 100(3): 287 - 291. [Abstract] [Full Text] [PDF]

				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]

				T. Kobayashi, T. Miyauchi, S. Sakai, M. Kobayashi, I. Yamaguchi, K. Goto, and Y. Sugishita Expression of endothelin-1, ETA and ETB receptors, and ECE and distribution of endothelin-1 in failing rat heart Am J Physiol Heart Circ Physiol, April 1, 1999; 276(4): H1197 - H1206. [Abstract] [Full Text] [PDF]

				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]

				B. Geny, F. Piquard, J. Lonsdorfer, and P. Haberey Endothelin and heart transplantation Cardiovasc Res, September 1, 1998; 39(3): 556 - 562. [Full Text] [PDF]

				K. Okada, Y. Nishida, H. Murakami, I. Sugimoto, H. Kosaka, H. Morita, C. Yamashita, and M. Okada Role of Endogenous Endothelin in the Development of Graft Arteriosclerosis in Rat Cardiac Allografts : Antiproliferative Effects of Bosentan, a Nonselective Endothelin Receptor Antagonist Circulation, June 16, 1998; 97(23): 2346 - 2351. [Abstract] [Full Text] [PDF]

				E. Thorin, P. Cernacek, and J. Dupuis Endothelin-1 Regulates Tone of Isolated Small Arteries in the Rat : Effect of Hyperendothelinemia Hypertension, April 1, 1998; 31(4): 1035 - 1041. [Abstract] [Full Text] [PDF]

				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]

				S. G. Greenberg, R. S. Baker, D. Yang, and K. E. Clark Effects of Continuous Infusion of Endothelin-1 in Pregnant Sheep Hypertension, December 1, 1997; 30(6): 1585 - 1590. [Abstract] [Full Text]

				C. R. Aversa, S. Oparil, J. Caro, H. Li, S.-D. Sun, Y.-F. Chen, M. R. Swerdel, T. M. Monticello, S. K. Durham, A. Minchenko, et al. Hypoxia stimulates human preproendothelin-1 promoter activity in transgenic mice Am J Physiol Lung Cell Mol Physiol, October 1, 1997; 273(4): L848 - L855. [Abstract] [Full Text] [PDF]

				P. Mulder, V. Richard, G. Derumeaux, M. Hogie, J. P. Henry, F. Lallemand, P. Compagnon, B. Mace, E. Comoy, B. Letac, et al. Role of Endogenous Endothelin in Chronic Heart Failure : Effect of Long-term Treatment With an Endothelin Antagonist on Survival, Hemodynamics, and Cardiac Remodeling Circulation, September 16, 1997; 96(6): 1976 - 1982. [Abstract] [Full Text]

				M. P. Love, W. G. Haynes, G. A. Gray, D. J. Webb, and J. J.V. McMurray Vasodilator Effects of Endothelin-Converting Enzyme Inhibition and Endothelin ETA Receptor Blockade in Chronic Heart Failure Patients Treated With ACE Inhibitors Circulation, November 1, 1996; 94(9): 2131 - 2137. [Abstract] [Full Text]

				C. R. Cannan, J. C. Burnett Jr, and A. Lerman Enhanced Coronary Vasoconstriction to Endothelin-BReceptor Activation in Experimental Congestive Heart Failure Circulation, February 15, 1996; 93(4): 646 - 651. [Abstract] [Full Text]

				S. Aharinejad, D. E. Schraufnagel, A. Miksovsky, E. K. Larson, and S. C. Marks Jr. Endothelin-1 focally constricts pulmonary veins in rats J. Thorac. Cardiovasc. Surg., July 1, 1995; 110(1): 148 - 156. [Abstract] [Full Text]

				K. A. H. Kaasjager, H. A. Koomans, and T. J. Rabelink Effectiveness of Enalapril Versus Nifedipine to Antagonize Blood Pressure and the Renal Response to Endothelin in Humans Hypertension, April 1, 1995; 25(4): 620 - 625. [Abstract] [Full Text]