Several cardiovascular disorders, including atherosclerosis, are associated with endothelial dysfunction and enhanced expression of endothelin-1 (ET-1). The role of ET-1 in the development of endothelial dysfunction in vivo remains unclear. The objective of the present study was to investigate the effect of elevated circulating levels of ET-1 on endothelium-dependent vasodilatation (EDV), and to test the hypothesis that ETA receptor antagonism improves EDV in patients with atherosclerosis. EDV and endothelium-independent vasodilatation were determined by brachial artery infusion of acetylcholine and sodium nitroprusside respectively during measurement of forearm blood flow (FBF) with venous occlusion plethysmography. A 60min intra-arterial infusion of ET-1 (n = 10) significantly blunted EDV in young healthy males (33±13% compared with 271±74% increase in FBF induced by 10μg/min acetylcholine; P < 0.01). Noradrenaline, which evoked a similar degree of vasoconstriction, did not attenuate EDV. In a separate set of experiments, a 60min intra-arterial infusion of the selective ETA receptor antagonist BQ123 evoked a significant increase in EDV in patients with atherosclerosis (n = 10; 109±45% compared with 255±101% increase in FBF induced by 10μg/min acetylcholine; P < 0.01), whereas no significant change was observed in healthy age-matched controls (n = 9). Endothelium-independent vasodilatation was not affected by ET-1 or BQ123. These observations demonstrate that elevated levels of ET-1 impair EDV in healthy control subjects. Furthermore, ETA receptor blockade improves EDV in patients with atherosclerosis, indicating that ET-1 attenuates EDV via an ETA-receptor-mediated mechanism.
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Research Article|
February 12 2002
Endothelin-1 inhibits endothelium-dependent vasodilatation in the human forearm: reversal by ETA receptor blockade in patients with atherosclerosis
Felix BÖHM;
*Department of Cardiology, Karolinska Hospital, S-171 76 Stockholm, Sweden
Correspondence: Dr Felix Böhm (e-mail Felix.Bohm@medks.ki.se).
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Gunvor AHLBORG;
Gunvor AHLBORG
†Department of Clinical Physiology, Huddinge Hospital, S-141 86 Huddinge, Sweden
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John PERNOW
John PERNOW
*Department of Cardiology, Karolinska Hospital, S-171 76 Stockholm, Sweden
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Publisher: Portland Press Ltd
Received:
July 09 2001
Revision Received:
September 19 2001
Accepted:
November 08 2001
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society and the Medical Research Society © 2002
2002
Clin Sci (Lond) (2002) 102 (3): 321–327.
Article history
Received:
July 09 2001
Revision Received:
September 19 2001
Accepted:
November 08 2001
Citation
Felix BÖHM, Gunvor AHLBORG, John PERNOW; Endothelin-1 inhibits endothelium-dependent vasodilatation in the human forearm: reversal by ETA receptor blockade in patients with atherosclerosis. Clin Sci (Lond) 1 March 2002; 102 (3): 321–327. doi: https://doi.org/10.1042/cs1020321
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