Differential effects of quinaprilat and enalaprilat on endothelial function of conduit arteries in patients with chronic heart failure

Citation
B. Hornig et al., Differential effects of quinaprilat and enalaprilat on endothelial function of conduit arteries in patients with chronic heart failure, CIRCULATION, 98(25), 1998, pp. 2842-2848
Citations number
30
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Journal title
CIRCULATION
ISSN journal
0009-7322 → ACNP
Volume
98
Issue
25
Year of publication
1998
Pages
2842 - 2848
Database
ISI
SICI code
0009-7322(199812)98:25<2842:DEOQAE>2.0.ZU;2-H
Abstract
Background-Chronic heart failure (CHF) is associated with endothelial dysfu nction, including impaired flow-dependent (endothelium-mediated) dilation ( FDD). We have previously shown that ACE inhibition improves endothelium-med iated vasodilation in healthy volunteers. The present study was designed to determine whether ACE inhibition improves the impaired FDD in patients wit h CHF. Because their affinity to tissue ACE may influence the ability of AC E inhibitors to affect endothelial function, we compared the effects of qui naprilat (high affinity to tissue ACE) and enalaprilat (low affinity to tis sue ACE) on FDD in patients with CHF. Methods and Results-High-resolution ultrasound and Doppler were used to mea sure radial artery diameter and blood flow in patients with CHF. The effect s of intra-arterial infusion of quinaprilat 1.6 mu g/min (n=15) and enalapr ilat 5 mu g/min (n=15) were determined at rest and during reactive hyperemi a (causing endothelium-mediated dilation) before and after N-monomethyl-L-a rginine (L-NMMA) to inhibit endothelial synthesis of nitric oxide. Quinapri lat improved FDD by >40% (10.2+/-0.6% Versus 6.9+/-0.6%; P<0.01), whereas e nalaprilat had no effect. In particular, the part of FDD mediated by nitric oxide (ie, inhibited by L-NMMA) was increased by >100% with quinaprilat (5 .6+/-0.5% versus 2.5+/-0.5%; P<0.01). Enalaprilat had no effect on FDD even when it was infused twice in the same dose (5 mu g/min) and up to 30 mu g/ min. The effect of sodium nitroprusside on radial artery diameter and blood flow was similar in patients treated with quinaprilat, enalaprilat, and pl acebo. Conclusions-Quinaprilat improves FDD in patients with CHF as the result of increased availability of nitric oxide, whereas enalaprilat does not. This observation suggests that intrinsic differences exist between quinaprilat a nd enalaprilat that determine the ability to improve endothelium-mediated v asodilation, ie, their different affinity to tissue ACE.