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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:674.)
© 2002 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Combined Endothelin Receptor Blockade Evokes Enhanced Vasodilatation in Patients With Atherosclerosis

Felix Böhm; Gunvor Ahlborg; Bo-Lennart Johansson; Lars-Olof Hansson; John Pernow

From the Department of Cardiology (F.B., J.P.), the Department of Surgical Sciences, Division of Clinical Physiology (B.-L.J.), and the Department of Clinical Chemistry (L.-O.H.), Karolinska Hospital, and the Department of Clinical Physiology (G.A.), Huddinge Hospital, Huddinge, Sweden.

Correspondence to Felix Böhm, MD, Department of Cardiology, Karolinska Hospital, S-171 76 Stockholm, Sweden. E-mail Felix.Bohm{at}medks.ki.se

Endothelin (ET)-1 causes vasoconstriction via ET_A and ET_B receptors located on vascular smooth muscle cells and vasodilatation via ET_B receptors on endothelial cells. Studies in vitro indicate an upregulation of ET_B receptors in atherosclerosis. The present study investigated the vascular effects evoked by endogenous ET-1 in atherosclerotic patients. Forearm blood flow (FBF) was measured with venous occlusion plethysmography in 10 patients with atherosclerosis and in 10 healthy control subjects during intra-arterial infusion of selective ET receptor antagonists. The ET_B receptor antagonist BQ788 evoked a significant increase in FBF (31±13%) in the patients, whereas a 20±9% reduction was observed in the control subjects. The ET_A receptor antagonist BQ123 combined with BQ788 evoked a marked increase in FBF (102±25%) in the patients compared with no effect in the control subjects (-3±9%, P<0.001 versus patients). The ET_A receptor antagonist BQ123 increased FBF to a similar degree in patients (39±11%) as in control subjects (41±11%). The increase in FBF evoked by selective ET_A receptor blockade was significantly (P<0.05) less than that evoked by combined ET_A/ET_B receptor blockade in the atherosclerotic patients. These observations suggest an enhanced ET-1–mediated vascular tone in atherosclerotic patients, which is at least partly due to increased ET_B-mediated vasoconstriction.

Key Words: endothelin • receptors • regional blood flow • atherosclerosis

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