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.
Skip Nav Destination
Close
Article navigation
March 2002
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).
Search for other works by this author on:
Gunvor AHLBORG
;
Gunvor AHLBORG
†Department of Clinical Physiology, Huddinge Hospital, S-141 86 Huddinge, Sweden
Search for other works by this author on:
John PERNOW
John PERNOW
*Department of Cardiology, Karolinska Hospital, S-171 76 Stockholm, Sweden
Search for other works by this author on:
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
Download citation file:
Close
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Biochemical Society Member Sign in
Sign InSign in via your Institution
Sign in via your InstitutionGet Access To This Article
6
Views
0
Citations
Cited By
Related Articles
Redistribution of Regional Blood Flow after Administration of Saralasin in Salt-Depleted Dogs
Clin Sci Mol Med (December,1978)
Noradrenaline and Nω-monomethyl-L-arginine (L-NMMA): effects on haemodynamics and regional blood flow in healthy and septic sheep
Clin Sci (Lond) (January,2000)
Positive inotropic responses mediated by endothelin ETA and ETB receptors in human myocardial trabeculae
Clin Sci (Lond) (August,2000)
Isolation of Human Cardiac Endothelin Receptors by a Peptide-Receptor Mobility Shift Assay
Clin Sci (Lond) (August,1993)