AT1-Receptor Antagonism Improves Endothelial Function in Coronary Artery Disease by a Bradykinin/B2-Receptor-Dependent Mechanism

ABSTRACT—Impaired flow-dependent, endothelium-mediated vasodilation is an early finding in patients with coronary artery disease (CAD). Experimental and some clinical studies observed that angiotensin type-1 receptor antagonists (AT1A) enhance endothelium-dependent relaxation in CAD. The present study was designed to determine whether AT1A improves flow-dependent dilation (FDD) in patients with CAD and, if so, whether bradykinin and NO are involved. High-resolution ultrasound was used to measure radial artery diameter at rest and during reactive hyperemia, causing endothelium-mediated vasodilation. Twenty patients with CAD were randomly assigned to receive intrabrachial infusion of candesartan (800 μg/min) with and without icatibant, a bradykinin B2-receptor antagonist (90 μg/min; group A) or N-monomethyl-l-arginine (L-NMMA), an NO-synthase inhibitor (7 μmol/min; group B). The AT1A candesartan improved FDD by >40%, an effect that was inhibited by icatibant (group Acontrol, 7.3±0.9; candesartan, 10.3±1.1; candesartan+icatibant, 5.0±0.5%). Similarly, L-NMMA blunted the beneficial effect of candesartan (group Bcontrol, 6.3±0.6; candesartan, 8.9±0.6; candesartan+L-NMMA4.7±0.5%; each P