title: AT1-receptor blockade with irbesartan improves peripheral but not coronary endothelial dysfunction in patients with stable coronary artery disease.
abstract: Activation of the renin-angiotensin-aldosterone system plays an important role in the pathogenesis of endothelial dysfunction and atherosclerosis. Studies evaluating the effect of AT1-receptor blockers on endothelial dysfunction in patients with coronary artery disease (CAD) revealed mixed results. Studies addressing the effects of AT1-receptor blockers on the coronary and peripheral function in the same study population, are still lacking. We therefore aimed to test the effects of long-term therapy with the AT1-receptor blocker irbesartan (IRB) on both, the coronary and peripheral endothelial function in patients with CAD. Seventy-two patients with CAD were randomly assigned to double-blinded treatment for 6 months with IRB 300 mg per day or placebo, respectively. Coronary and peripheral endothelial function were measured by intracoronary infusion of acetylcholine (final intracoronary concentration 10(-7.3) to 10(-5.6)M) and by determining flow-dependent dilation (FMD) of the brachial artery, respectively. IRB significantly improved FMD, while no change of coronary endothelial function was observed. Interestingly, plasma levels of N(G),N(G)-dimethyl-arginine, and the isoprostane excretion rate were not modified. IRB treatment improves peripheral but not coronary endothelial dysfunction in patients with CAD. Since reduced FMD of the brachial artery has been shown to be associated with a high-cardiovascular event rate, improvement of FMD by IRB may lead to better prognosis of patients with CAD.
authors.affiliation: Department of Medicine II, Johannes Gutenberg-University Mainz, Langenbeckstrasse 1, 55101 Mainz, Germany. warnholt@uni-mainz.de
authors.forename: Ascan
authors.initials: A
authors.lastname: Warnholtz
authors.forename: Mir Abolfazl
authors.initials: MA
authors.lastname: Ostad
authors.forename: Thomas
authors.initials: T
authors.lastname: Heitzer
authors.forename: Felix
authors.initials: F
authors.lastname: Thuneke
authors.forename: Meike
authors.initials: M
authors.lastname: Fröhlich
authors.forename: Peter
authors.initials: P
authors.lastname: Tschentscher
authors.forename: Edzard
authors.initials: E
authors.lastname: Schwedhelm
authors.forename: Rainer
authors.initials: R
authors.lastname: Böger
authors.forename: Thomas
authors.initials: T
authors.lastname: Meinertz
authors.forename: Thomas
authors.initials: T
authors.lastname: Munzel
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D001916:Brachial Artery / Q000187:drug effects* / Q000502:physiology; D003324:Coronary Artery Disease / Q000188:drug therapy*; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000187:drug effects; D005260:Female; D006801:Humans; D000077405:Irbesartan; D008297:Male; D008875:Middle Aged; D012039:Regional Blood Flow / Q000187:drug effects; D013777:Tetrazoles / Q000627:therapeutic use*; D014463:Ultrasonography; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D013777:Tetrazoles; D000077405:Irbesartan