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Experimental Biology and Medicine 231:857-860 (2006)
© 2006 Society for Experimental Biology and Medicine

HEART

Beneficial Cardiovascular Effects of Endothelin ETA Receptor Blockade in Established Long-Term Heart Failure After Myocardial Infarction

Diana Vetter*, Sidney G. Shaw{dagger}, Ralf P. Brandes{ddagger}, Klaus MüNter§, Wilhelm Vetter* and Matthias Barton*,1

* Medizinische Poliklinik, Universitätsspital, Zürich, Switzerland; {dagger} Department of Clinical Research, University Hospital, Bern, Switzerland; {ddagger} Zentrum für Kardiovaskuläre Physiologie, Klinikum der J.-W. Goethe Universität, Frankfurt, Germany; and § Cardiovascular II, Bayer AG, Wuppertal, Germany

To whom requests for reprints should be addressed at 1 Medizinische Poliklinik, Universitätsspital Zürich, Rämistrasse 100, CH-8091 Zürich, Switzerland. E-mail: barton{at}usz.ch

Abstract

Although experimental prevention studies have suggested therapeutic potential of endothelin (ET) antagonists for the treatment of heart failure, the results of clinical trials using ET antagonists on top of standard heart failure medications have been largely disappointing. This experimental study investigated the effects of chronic ETA receptor blockade in long-term survivors of myocardial infarction who had developed stable chronic heart failure in the absence of other treatments. Systolic blood pressure, heart rate, organ weights of the right atrium and ventricle, and the lungs were determined, and tissue ET-1 peptide levels were measured in cardiac tissue, lung, and aorta. The results show that chronic blockade of ETA receptors stabilizes systolic blood pressure and reverses the heart failure–induced weight increases of right heart chambers and lung. The changes observed occurred independently of tissue ET-1 concentrations and heart rate, suggesting mechanisms independent of local cardiac or pulmonary ET-1 synthesis, which are yet to be identified.

Key Words: chronic • heart • blood pressure • remodeling • right atrium • right ventricle • lung






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Copyright © 2006 by the Society for Experimental Biology and Medicine.