Cardiac preload reduction through venodilatation is beneficial in chronic heart failure. The recent development of endothelin receptor antagonists for possible therapeutic use in heart failure has hastened the need for a clearer understanding of the venoconstrictor actions of endothelin-1 in this disease. Two main subtypes of endothelin receptor, ETA and ETB, exist in human blood vessels. We studied the venoconstrictor effects of endothelin-1 (a non-selective ETA and ETB agonist) and sarafotoxin S6c (a selective ETB agonist) in vivo in patients with chronic heart failure and in age-matched healthy controls. On separate days at least 1 week apart, locally active doses of endothelin-1 or sarafotoxin S6c were infused into a suitable dorsal hand vein for 1 h, and the venous internal diameter was measured using a displacement technique. Venoconstriction in response to endothelin-1 was significantly blunted in heart failure patients compared with controls (26±7% and 51±6% peak reduction in vein calibre respectively; P = 0.013). Venoconstriction to sarafotoxin S6c was similar in heart failure patients and controls (17±5% and 17±4% peak reduction in vein calibre respectively). Both ETA and ETB receptors mediate venoconstriction in healthy subjects and in patients with chronic heart failure. Optimal inhibition of the venoconstrictor effects of endothelin-1 in chronic heart failure may therefore require administration of an antagonist with ETA- and ETB-receptor-blocking properties. Chronic heart failure may be associated with a selective decrease in venous ETA receptor sensitivity, but further studies are required to clarify the functional significance of this observation.
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Research Article|
November 22 1999
Venous endothelin receptor function in patients with chronic heart failure
Michael P. LOVE;
*Department of Cardiology, Western General Hospital, Edinburgh EH4 2XU, Scotland, U.K.
Correspondence: Dr M. P. Love, Department of Medical Cardiology, Glasgow Royal Infirmary, Alexandra Parade, Glasgow G31 2ER, Scotland, U.K. (e-mail [email protected]).
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William G. HAYNES;
William G. HAYNES
†Department of Medicine, Western General Hospital, Edinburgh EH4 2XU, Scotland, U.K.
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David J. WEBB;
David J. WEBB
†Department of Medicine, Western General Hospital, Edinburgh EH4 2XU, Scotland, U.K.
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John J. V. MCMURRAY
John J. V. MCMURRAY
*Department of Cardiology, Western General Hospital, Edinburgh EH4 2XU, Scotland, U.K.
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Publisher: Portland Press Ltd
Received:
May 14 1999
Revision Received:
July 23 1999
Accepted:
September 08 1999
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society and the Medical Research Society © 1999
1999
Clin Sci (Lond) (2000) 98 (1): 65–70.
Article history
Received:
May 14 1999
Revision Received:
July 23 1999
Accepted:
September 08 1999
Citation
Michael P. LOVE, William G. HAYNES, David J. WEBB, John J. V. MCMURRAY; Venous endothelin receptor function in patients with chronic heart failure. Clin Sci (Lond) 1 January 2000; 98 (1): 65–70. doi: https://doi.org/10.1042/cs0980065
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