Published Online
on March 24, 2003

A more recent version of this article appeared on May 1, 2003

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Submitted on January 24, 2003
Revised on February 17, 2003

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; and Helmut Drexler

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

^* To whom correspondence should be addressed. E-mail: Hornig.Burkhard{at}mh-hannover.de.

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 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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