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(Circulation. 2001;103:981.)
© 2001 American Heart Association, Inc.

Clinical Investigation and Reports

Effects of Endothelin A Receptor Blockade on Endothelial Function in Patients With Chronic Heart Failure

Rudolf Berger, MD; Brigitte Stanek, MD; Martin Hülsmann, MD; Bernhard Frey, MD; Sandra Heher, MD; Richard Pacher, MD; Thomas Neunteufl, MD

From the Department of Cardiology, University of Vienna, Austria.

Correspondence to Thomas Neunteufl, MD, Department of Cardiology, University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria. Email thomas.neunteufl{at}univie.ac.at

Background—Chronic heart failure (CHF) is associated with impaired endothelium-dependent vasodilation and increased basal vascular tone due, in part, to elevated endothelin-1 plasma levels. In the present study, we investigated whether a reduction of vascular tone using an endothelin A receptor blocker attenuates the impairment of endothelium-dependent, flow-mediated vasodilation (FMD).

Methods and Results—Twenty-one patients with CHF randomly received either the endothelin A receptor blocker LU 135252 (30 mg/d, n=7; 300 mg/d, n=7) or a placebo (n=7). Using high-resolution ultrasound, FMD and endothelium-independent, nitroglycerin-induced dilation of the brachial artery were assessed at baseline in the 21 patients with CHF and in 11 controls and after 3 weeks treatment in the 21 patients with CHF. FMD at baseline was impaired in all 21 patients with CHF (3.2±2%) when compared with the 11 controls (9.7±4.9%; P=0.0005). In comparison with baseline, FMD significantly improved after 3 weeks of treatment with LU 135252 in all 14 patients receiving it (from 3.0±2.0% to 4.9±2.9%; P=0.04), but FMD remained unchanged with placebo. Subgroup analysis, according to different dosages, revealed a significant increase of FMD compared with baseline (from 2.4±1.5% to 5.5±2.4%; P=0.03) in the patients treated with the low-dose (30 mg/d), whereas a high dose of 300 mg/d failed to increase FMD significantly. Improvement in the high-dose group, however, may have been masked by reduced vasodilator capacity due to a significant increase in vessel size (from 4.8±0.4 to 5.1±0.7 mm; P=0.03).

Conclusions—These results suggest that endothelin A receptor blockade improves FMD in CHF patients.

Key Words: heart failure • endothelin • endothelium

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