Effects of endothelin A receptor blockade on endothelial function in patients with chronic heart failure

Backgound-Chronic heart failure (CHF) is associated with impaired endotheli um-dependent vasodilation and increased basal vascular tone due, in part, t o elevated endothelin-l plasma levels. In the present study, we investigate d whether a reduction of vascular tone using an endothelin A receptor block er attenuates the impairment of endothelium-dependent, flow-mediated vasodi lation (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) o r a placebo (n=7). Using high-resolution ultrasound, FMD and endothelium-in dependent, nitroglycerin-induced dilation of the brachial artery were asses sed 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 i n 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 impr oved 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 w ith 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), wher eas a high dose of 300 mg/d failed to increase FMD significantly. Improveme nt in the high-dose group, however, may have been masked by reduced vasodil ator 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 impro ves FMD in CHF patients.