Endogenous endothelin in human coronary vascular function: differential contribution of endothelin receptor types A and B

Halcox, Julian P.J., Nour, Khaled R.A., Zalos, Gloria and Quyyumi, Arshed A. 2007. Endogenous endothelin in human coronary vascular function: differential contribution of endothelin receptor types A and B. Hypertension 49 (5) , pp. 1134-1141. 10.1161/hypertensionaha.106.083303

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Abstract

Endothelin 1 mediates coronary vasoconstriction and endothelial dysfunction via endothelin receptor type A (ET(A)) activation. However, the effects of selective endothelin receptor type B (ET(B)) and combined ET(A+B) receptor blockade on coronary vasomotion are unknown. We measured coronary vascular tone and endothelium-dependent and -independent vasomotor function before and after selective infusion of BQ-788 (an ET(B) receptor antagonist) or combined infusion of BQ-788+BQ-123 (an ET(A) antagonist) into unobstructed coronary arteries of 39 patients with coronary atherosclerosis or risk factors undergoing cardiac catheterization. BQ-788 did not affect epicardial diameter but constricted the microcirculation (P<0.0001), increased coronary sinus endothelin, and reduced nitrogen oxide levels. In contrast, BQ-123+BQ-788 dilated epicardial (P<0.0001) and resistance (P=0.022) arteries. Responses to acetylcholine and sodium nitroprusside were unaffected by BQ-788 alone. Epicardial endothelial dysfunction improved after BQ-123+BQ-788 (P=0.007). Coronary microvascular responses to acetylcholine and sodium nitroprusside were unaffected by BQ-123+BQ-788. We conclude that selective ET(B) receptor antagonism causes coronary microvascular constriction, without affecting epicardial tone or endothelial function, via reduced endothelin clearance and NO availability. Combined ET(A+B) blockade dilates coronary conduit and resistance vessels and improves endothelial dysfunction of the epicardial coronary arteries. Thus, endogenous endothelin, predominantly via ET(A) receptor stimulation, contributes to basal constrictor tone and endothelial dysfunction, whereas ET(B) activation mediates vasodilation in human coronaries. Our data suggest that selective ET(A) blockade may have greater therapeutic potential than nonselective agents, particularly for treatment of endothelial dysfunction in atherosclerosis.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Medicine
Subjects:	R Medicine > R Medicine (General)
Additional Information:	Full Text Sources HighWire Ovid Technologies, Inc. Other Literature Sources COS Scholar Universe Labome Researcher Resource - ExactAntigen/Labome Access more work from the authors - ResearchGate Medical EDNRB Gene - Genetics Home Reference Coronary Artery Disease - MedlinePlus Health Information
Publisher:	American Heart Association
ISSN:	0194-911X
Date of Acceptance:	20 February 2007
Last Modified:	02 Nov 2015 10:24
URI:	https://orca.cardiff.ac.uk/id/eprint/70594

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