© 2004 European Society of Cardiology
Comparison of selective ETA and ETB receptor antagonists in patients with chronic heart failure
a Wessex Cardiothoracic Centre, Southampton General Hospital Mailpoint 46, Tremona Road, Southampton, SO16 6YD, UK
b Department of Cardiology, Castle Hill Hospital, University of Hull Kingston upon Hull HU5 7RX, UK
c Royal Brampton Hospital Sydney Street, London, SW3 6NP, UK
d Department of Cardiology, Western Infirmary Glasgow G11 6NT, UK
e Medical Research Council Clinical Research Initiative in Heart Failure University of Glasgow, Glasgow G12 8QQ, UK
* Corresponding author. Tel.: +44 2380 777222; fax: +44 2380 796352. E-mail address: pjcowburn{at}hotmail.com
 |
Abstract |
|---|
Background: The vasoconstrictor action of endothelin-1 (ET-1) is mediated through ETA and ETB receptor subtypes on vascular smooth muscle. ETB receptors are also present on the vascular endothelium where they mediate vasodilation. Animal studies suggest that the ETB receptor also acts as a clearance receptor for endothelin.
Aims: To investigate the effects of a selective ETA and a selective ETB receptor antagonist alone and in combination on haemodynamics and circulating concentrations of ET-1 in patients with chronic heart failure.
Results: Infusion of BQ-123 (n=10), a selective ETA receptor antagonist, led to systemic vasodilation and did not change plasma ET-1 concentrations (1.38±0.82 to 1.38±0.91 fmol/ml, ns). Infusion of BQ-788 (n=8) led to systemic vasoconstriction with a rise in plasma ET-1 (1.84±1.06 to 2.73±0.99 fmol/ml, p<0.01). The addition of BQ-123 to BQ-788 led to systemic and pulmonary vasodilation with no further increase in plasma ET-1 concentrations (2.80±1.14 to 2.90±1.20 fmol/ml, ns).
Conclusion: The rise in plasma ET-1 concentrations in response to selective blockade of ETB receptors and the associated adverse haemodynamic effects suggest that ETB receptors have a role in the clearance of ET-1 in man and that their blockade may not be advantageous for patients with heart failure.
Key Words: Endothelins • Heart failure • Pulmonary circulation
Received August 4, 2004; Accepted August 18, 2004
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  L. E. Kandalaft, A. Facciabene, R. J. Buckanovich, and G. Coukos Endothelin B Receptor, a New Target in Cancer Immune Therapy Clin. Cancer Res., July 15, 2009; 15(14): 4521 - 4528. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Ahlborg, A. Shemyakin, F. Bohm, A. Gonon, and J. Pernow Dual Endothelin Receptor Blockade Acutely Improves Insulin Sensitivity in Obese Patients With Insulin Resistance and Coronary Artery Disease Diabetes Care, March 1, 2007; 30(3): 591 - 596. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N F Kelland and D J Webb Clinical trials of endothelin antagonists in heart failure: publication is good for the public health Heart, January 1, 2007; 93(1): 2 - 4. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Battistini, N. Berthiaume, N. F. Kelland, D. J. Webb, and D. E. Kohan Profile of Past and Current Clinical Trials Involving Endothelin Receptor Antagonists: The Novel "-Sentan" Class of Drug. Experimental Biology and Medicine, June 1, 2006; 231(6): 653 - 695. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. F. Kelland and D. J. Webb Clinical Trials of Endothelin Antagonists in Heart Failure: A Question of Dose? Experimental Biology and Medicine, June 1, 2006; 231(6): 696 - 699. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. F. Pauly Cardiac Function and Heart Failure J. Am. Coll. Cardiol., June 7, 2005; 45(11_Suppl_B): B24 - B29. [Full Text] [PDF]
|
|