Investigation of the Endothelin System in Experimental Heart Failure

  • Gillian A. Gray
  • Lorcan Sherry
Part of the Methods in Molecular Biology™ book series (MIMB, volume 206)


The first evidence that endothelin-1 (ET-1) was implicated in the pathophysiology of chronic heart failure (CHF) came from studies demonstrating elevated plasma concentrations of the mature peptide in patients with CHF (1) Subsequent studies showed that plasma levels of ET-1 and particularly of its precursor big ET-1 correlated with the severity of CHF (2) and were able to predict the necessity for heart transplant (3). The ET system has since been studied in CHF patients using acute administration of inhibitors of ET formation, ET receptor agonists and ET receptor antagonists either locally into the forearm or hand vein (4,5, see  Chapter 14) or systemically (6,7). These hemodynamic studies provided an indication that blockade of the ET system might be of therapeutic benefit in CHF. However, these types of studies are unable to answer questions relating to tissue expression of the ET-1 synthesizing pathway or ET receptors and how these might be altered during disease progression. These questions can be best addressed initially using experimental models, which also permit detailed histological and molecular analysis of the pathways modified by ET system blockade and can be followed through to a mortality endpoint. Studies in experimental animals provided the first evidence that ET receptor antagonists might improve survival in heart failure (8) and these observations are now being followed through into clinical trials in CHF patients (9).


Chronic Heart Failure Infarct Size Chronic Heart Failure Patient Ventricular Free Wall Coronary Artery Ligation 
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Copyright information

© Humana Press Inc. 2002

Authors and Affiliations

  • Gillian A. Gray
    • 1
  • Lorcan Sherry
    • 2
  1. 1.Endothelial Cell Biology and Molecular Cardiology Group, Centre for Cardiovascular Sciences, Division of Biomedical and Clinical Laboratory SciencesUniversity of EdinburghEdinburghUK
  2. 2.Research and DevelopmentOrganon Laboratories Ltd.NewhouseUK

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