ABSTRACT
On the basis of complete blockade of endothelin-A (ET-A) receptor,the hemodynamic effects of further removal of endothelin-B receptor mediated effect with endothelin converting enzyme is not clear.We studied forearm vasodilation (with plethysmography) during a maximally effective dose of an ET-A receptor antagonist alone (brachial artery infusion of BQ123,36μg/min*100mL tissue for 25min) and during double blind,randomized,additional endothelin converting enzyme inhibition (phosphoramidon,20μg/min*100mL tissue for 15min,n=6) or placebo (n=6) in 12 patients with severe congestive heart failure (CHF).Baseline clinical characteristics in terms of age,NYHA grade,LVEF and medications are comparable between the two groups.As a study control,we carried out the same protocol in 12 normal volunteers.Forearm blood flow (FBF) increased similarly in patient with CHF and in normal volunteers after BQ123 over the 45 min observation period.There were significant further increases of FBF in both study populations after phosphoramidon infusion.While in placebo treated CHF patients during the additional 45min observation period,there is a decrease of FBF by a mean of 30% (mean difference between Phosph and Pla 57%,95% CI 43 to 72%,P＜0.001),which was greater than that in normal subjects.In patients with severe CHF as well as in normal volunteers,endothelin converting enzyme inhibition results in further vasodilation on the basis of ET-A receptor blockade alone,which suggests that ET-B receptor may play a role in maintaining vascular tong in human beings.