Koh Kwang Kon, Quon Michael J, Han Seung Hwan, Chung Wook-Jin, Kim Jeong-A, Shin Eak Kyun
Division of Cardiology, Gil Heart Center, Gachon Medical School, Incheon, Korea.
J Hypertens Suppl. 2006 Mar;24(1):S31-8. doi: 10.1097/01.hjh.0000220404.38622.6a.
Effects of angiotensin II type 1 receptor blockers (ARBs) to improve endothelial dysfunction may be due to mechanisms in addition to the reduction of high blood pressure per se. Endothelial dysfunction is characterized by vascular inflammation that contributes to clinically significant atherosclerosis and by an increased tendency for thrombus formation. Hypertensive patients have impaired endothelial functions that have positive predictive power with respect to future cardiovascular events.
The present review will focus on multiple mechanisms underlying vascular and metabolic effects of ARBs that may synergize to prevent or regress atherosclerosis, onset of diabetes, and coronary heart disease.
Angiotensin II accelerates the development of atherosclerosis by activating angiotensin II type 1 receptors that then promote superoxide anion generation and oxidative stress, leading to activation of nuclear transcription factor and endothelial dysfunction. Activation of angiotensin II type 1 receptors also stimulates increased expression of plasminogen activator inhibitor type 1 and tissue factor. Endothelial dysfunction associated with the metabolic syndrome and other insulin-resistant states is characterized by impaired insulin-stimulated production of nitric oxide from the endothelium and decreased blood flow to skeletal muscle. Increasing insulin sensitivity therefore improves endothelial function, and this may be an additional mechanism whereby ARBs decrease the incidence of coronary heart disease and the onset of diabetes. Adiponectin serves to link obesity with insulin resistance. In addition, adiponectin has anti-atherogenic properties.
血管紧张素II 1型受体阻滞剂（ARB）改善内皮功能障碍的作用可能归因于除降低高血压本身之外的机制。内皮功能障碍的特征是血管炎症（其促成具有临床意义的动脉粥样硬化）以及血栓形成倾向增加。高血压患者存在内皮功能受损，这对未来心血管事件具有阳性预测能力。
本综述将聚焦于ARB血管和代谢作用的多种潜在机制，这些机制可能协同作用以预防或逆转动脉粥样硬化、糖尿病发病及冠心病。
血管紧张素II通过激活血管紧张素II 1型受体加速动脉粥样硬化的发展，该受体随后促进超氧阴离子生成和氧化应激，导致核转录因子激活和内皮功能障碍。血管紧张素II 1型受体的激活还刺激纤溶酶原激活物抑制剂1型和组织因子表达增加。与代谢综合征及其他胰岛素抵抗状态相关的内皮功能障碍的特征是胰岛素刺激的内皮一氧化氮生成受损以及骨骼肌血流减少。因此，增加胰岛素敏感性可改善内皮功能，这可能是ARB降低冠心病发病率和糖尿病发病的另一机制。脂联素起到将肥胖与胰岛素抵抗联系起来的作用。此外，脂联素具有抗动脉粥样硬化特性。
