Warnholtz Ascan, Ostad Mir Abolfazl, Heitzer Thomas, Thuneke Felix, Fröhlich Meike, Tschentscher Peter, Schwedhelm Edzard, Böger Rainer, Meinertz Thomas, Munzel Thomas
Department of Medicine II, Johannes Gutenberg-University Mainz, Langenbeckstrasse 1, 55101 Mainz, Germany.
Atherosclerosis. 2007 Oct;194(2):439-45. doi: 10.1016/j.atherosclerosis.2006.08.034. Epub 2006 Sep 12.
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.
肾素-血管紧张素-醛固酮系统的激活在血管内皮功能障碍和动脉粥样硬化的发病机制中起重要作用。评估血管紧张素Ⅱ1型受体（AT1）阻滞剂对冠心病（CAD）患者血管内皮功能障碍影响的研究结果不一。在同一研究人群中探讨AT1阻滞剂对冠状动脉和外周功能影响的研究尚缺。因此，我们旨在测试AT1阻滞剂厄贝沙坦（IRB）长期治疗对CAD患者冠状动脉和外周血管内皮功能的影响。72例CAD患者被随机分为两组，分别接受每天300mg IRB或安慰剂的双盲治疗6个月。冠状动脉和外周血管内皮功能分别通过冠状动脉内注射乙酰胆碱（冠状动脉内最终浓度为10^(-7.3)至10^(-5.6)M）和测定肱动脉血流介导的舒张功能（FMD）来评估。IRB显著改善了FMD，但未观察到冠状动脉内皮功能的变化。有趣的是，血浆中N(G),N(G)-二甲基精氨酸水平和异前列腺素排泄率未发生改变。IRB治疗可改善CAD患者的外周血管内皮功能障碍，但不能改善冠状动脉内皮功能障碍。由于肱动脉FMD降低已被证明与高心血管事件发生率相关，IRB改善FMD可能会改善CAD患者的预后。
