This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Berger, R. Articles by Neunteufl, T. Search for Related Content PubMed PubMed Citation Articles by Berger, R. Articles by Neunteufl, T. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Heart Failure Hazardous Substances DB NITROGLYCERIN Related Collections Heart failure - basic studies Endothelium/vascular type/nitric oxide

(Circulation. 2001;103:981.)
© 2001 American Heart Association, Inc.

Clinical Investigation and Reports

Effects of Endothelin A Receptor Blockade on Endothelial Function in Patients With Chronic Heart Failure

Rudolf Berger, MD; Brigitte Stanek, MD; Martin Hülsmann, MD; Bernhard Frey, MD; Sandra Heher, MD; Richard Pacher, MD; Thomas Neunteufl, MD

From the Department of Cardiology, University of Vienna, Austria.

Correspondence to Thomas Neunteufl, MD, Department of Cardiology, University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria. Email thomas.neunteufl{at}univie.ac.at

Background—Chronic heart failure (CHF) is associated with impaired endothelium-dependent vasodilation and increased basal vascular tone due, in part, to elevated endothelin-1 plasma levels. In the present study, we investigated whether a reduction of vascular tone using an endothelin A receptor blocker attenuates the impairment of endothelium-dependent, flow-mediated vasodilation (FMD).

Methods and Results—Twenty-one patients with CHF randomly received either the endothelin A receptor blocker LU 135252 (30 mg/d, n=7; 300 mg/d, n=7) or a placebo (n=7). Using high-resolution ultrasound, FMD and endothelium-independent, nitroglycerin-induced dilation of the brachial artery were assessed at baseline in the 21 patients with CHF and in 11 controls and after 3 weeks treatment in the 21 patients with CHF. FMD at baseline was impaired in all 21 patients with CHF (3.2±2%) when compared with the 11 controls (9.7±4.9%; P=0.0005). In comparison with baseline, FMD significantly improved after 3 weeks of treatment with LU 135252 in all 14 patients receiving it (from 3.0±2.0% to 4.9±2.9%; P=0.04), but FMD remained unchanged with placebo. Subgroup analysis, according to different dosages, revealed a significant increase of FMD compared with baseline (from 2.4±1.5% to 5.5±2.4%; P=0.03) in the patients treated with the low-dose (30 mg/d), whereas a high dose of 300 mg/d failed to increase FMD significantly. Improvement in the high-dose group, however, may have been masked by reduced vasodilator capacity due to a significant increase in vessel size (from 4.8±0.4 to 5.1±0.7 mm; P=0.03).

Conclusions—These results suggest that endothelin A receptor blockade improves FMD in CHF patients.

Key Words: heart failure • endothelin • endothelium

This article has been cited by other articles:

				M. Kooijman, D. H. J. Thijssen, P. C. E. de Groot, M. W. P. Bleeker, H. J. M. van Kuppevelt, D. J. Green, G. A. Rongen, P. Smits, and M. T. E. Hopman Flow-mediated dilatation in the superficial femoral artery is nitric oxide mediated in humans J. Physiol., February 15, 2008; 586(4): 1137 - 1145. [Abstract] [Full Text] [PDF]

				B. A. Parker, S. J. Ridout, and D. N. Proctor Age and flow-mediated dilation: a comparison of dilatory responsiveness in the brachial and popliteal arteries Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H3043 - H3049. [Abstract] [Full Text] [PDF]

				K. E Pyke and M. E Tschakovsky The relationship between shear stress and flow-mediated dilatation: implications for the assessment of endothelial function J. Physiol., October 15, 2005; 568(2): 357 - 369. [Abstract] [Full Text] [PDF]

				B. Meyer, D. Mortl, K. Strecker, M. Hulsmann, V. Kulemann, T. Neunteufl, R. Pacher, and R. Berger Flow-Mediated Vasodilation Predicts Outcome in Patients With Chronic Heart Failure: Comparison With B-Type Natriuretic Peptide J. Am. Coll. Cardiol., September 20, 2005; 46(6): 1011 - 1018. [Abstract] [Full Text] [PDF]

				M. E. Tschakovsky and K. E. Pyke Counterpoint: Flow-mediated dilation does not reflect nitric oxide-mediated endothelial function J Appl Physiol, September 1, 2005; 99(3): 1235 - 1237. [Full Text] [PDF]

				M. L. Bots, J. Westerink, T. J. Rabelink, and E. J.P. de Koning Assessment of flow-mediated vasodilatation (FMD) of the brachial artery: effects of technical aspects of the FMD measurement on the FMD response Eur. Heart J., February 2, 2005; 26(4): 363 - 368. [Abstract] [Full Text] [PDF]

				J. Gomez-Cerezo, J. J. Rios Blanco, I. Suarez Garcia, P. Moreno Anaya, P. Garcia Raya, E. Vazquez-Munoz, and F. J. Barbado Hernandez Noninvasive Study of Endothelial Function in White Coat Hypertension Hypertension, September 1, 2002; 40(3): 304 - 309. [Abstract] [Full Text] [PDF]

				A. V Agapitov and W. G Haynes Role of endothelin in cardiovascular disease Journal of Renin-Angiotensin-Aldosterone System, March 1, 2002; 3(1): 1 - 15. [Abstract] [PDF]

				C. Cardillo, U. Campia, C. M. Kilcoyne, M. B. Bryant, and J. A. Panza Improved Endothelium-Dependent Vasodilation After Blockade of Endothelin Receptors in Patients With Essential Hypertension Circulation, January 29, 2002; 105(4): 452 - 456. [Abstract] [Full Text] [PDF]

				T. O. Cheng Endothelin Receptor Blockade in Congestive Heart Failure Circulation, October 30, 2001; 104 (18): e96 - e96. [Full Text] [PDF]