Endothelin-1 (ET-1) has been proposed to contribute to the regulation of vascular tone in humans. BQ-123, an ETA receptor antagonist, has also been reported to increase forearm blood flow (FBF) in vivo; however, the efficacy of BQ-123 as an antagonist of ET-1 has not been evaluated in the forearm. The present study investigated the effects of BQ-123 on changes in FBF in response to ET-1 and noradrenaline (NA; norepinephrine), taking into account the possible influence of vasodilator effects of BQ-123 on responses to vasoconstrictors. Six subjects (age 25-34 years) participated in a double-blind randomized study. FBF was measured by forearm occlusion plethysmography. Drugs were infused intra-arterially into the non-dominant arm (study arm) on four separate occasions; the non-infused arm was used as a control. The effects of BQ-123 (50nmol/min for 60min, or 300nmol/min for 5min followed by saline for 55min) were compared with the effects of infusion of sodium nitroprusside (SNP; 12nmol/min for 60min) or saline on vasoconstriction induced by ET-1 (10pmol/min for 7min) and NA (120pmol/min for 7min). Infusion of BQ-123 at either dose did not significantly increase FBF, whereas SNP increased FBF by 134% (P = 0.03). ET-1 significantly reduced FBF, and this effect was almost completely inhibited by both doses of BQ-123, but was unaffected by SNP. NA also reduced FBF, and this action was unaffected by BQ-123 or SNP. The data show that BQ-123 is a selective ET-1 antagonist, but do not confirm a major role for ET-1 in influencing resting forearm vascular tone in young normotensive subjects.
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May 14 2002
Action of the endothelin receptor (ETA) antagonist BQ-123 on forearm blood flow in young normotensive subjects
R.C. WIMALASUNDERA;
*Clinical Pharmacology, NHLI, Imperial College School of Medicine, St Mary's Hospital, London W2 1NY, U.K.
Correspondence: Dr R.C. Wimalasundera, Centre For Fetal Care, Queen Charlotte's & Chelsea Hospital, Du Cane Road, London W12 0NN, U.K. (e-mail [email protected]).
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S.A.McG. THOM;
S.A.McG. THOM
*Clinical Pharmacology, NHLI, Imperial College School of Medicine, St Mary's Hospital, London W2 1NY, U.K.
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L. REGAN;
L. REGAN
†Obstetrics & Gynaecology, Imperial College School of Medicine, St Mary's Hospital, London W2 1NY, U.K.
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A.D. HUGHES
A.D. HUGHES
*Clinical Pharmacology, NHLI, Imperial College School of Medicine, St Mary's Hospital, London W2 1NY, U.K.
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Publisher: Portland Press Ltd
Received:
November 20 2001
Revision Received:
January 28 2002
Accepted:
March 15 2002
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society and the Medical Research Society © 2002
2002
Clin Sci (Lond) (2002) 102 (6): 661–666.
Article history
Received:
November 20 2001
Revision Received:
January 28 2002
Accepted:
March 15 2002
Citation
R.C. WIMALASUNDERA, S.A.McG. THOM, L. REGAN, A.D. HUGHES; Action of the endothelin receptor (ETA) antagonist BQ-123 on forearm blood flow in young normotensive subjects. Clin Sci (Lond) 1 June 2002; 102 (6): 661–666. doi: https://doi.org/10.1042/cs1020661
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