Combined Endothelin Receptor Blockade Evokes Enhanced Vasodilatation in Patients With Atherosclerosis

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Abstract
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 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 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.