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(Hypertension. 2003;41:1092.)
© 2003 American Heart Association, Inc.

Scientific Contributions

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

Burkhard Hornig; Christoph Kohler; Daniel Schlink; Helma Tatge; Helmut Drexler

From Abteilung Kardiologie und Angiologie, Zentrum Innere Medizin, Medizinische Hochschule Hannover, Hannover, Germany.

Correspondence to Burkhard Hornig, MD, Abteilung Kardiologie und Angiologie, Medizinische Hochschule Hannover, Carl Neuberg Str 1, 30625 Hannover, Germany. E-mail Hornig.Burkhard{at}mh-hannover.de

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 A: control, 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 B: control, 6.3±0.6; candesartan, 8.9±0.6; candesartan+L-NMMA: 4.7±0.5%; each P<0.01). The angiotensin type-1 receptor antagonist candesartan improves flow-dependent, endothelium-mediated vasodilation in patients with CAD. This effect is inhibited by either icatibant and or L-NMMA, suggesting that both bradykinin and NO contribute to the vascular effects of AT₁-receptor antagonists in this patient population.

Key Words: endothelium • angiotensin II • receptors, angiotensin II • angiotensin antagonist • bradykinin • nitric oxide

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