Landmesser Ulf, Drexler Helmut
Abteilung Kardiologie und Angiologie, Medizinische Hochschule Hannover, Hannover, Germany.
J Hypertens Suppl. 2006 Mar;24(1):S39-43. doi: 10.1097/01.hjh.0000220405.38622.23.
The important role of the endothelium for regulation of vascular tone, growth, inflammatory response, coagulation and thrombocyte adhesion has now been recognized. Endothelial function has largely been assessed as endothelium-dependent vasodilation, assuming that endothelium-dependent vasomotion represents a surrogate marker for other important endothelial functions. An important rational for this approach has been the observation that both endothelium-dependent vasomotion and other protective endothelial functions are at least partially mediated by nitric oxide. Accumulating clinical studies have now demonstrated a close and independent association of impaired endothelium-dependent vasodilation with cardiovascular events and prognosis. These findings have stimulated interest in treatment options to improve endothelial function in patients at high cardiovascular risk.
This article describes recent insights into endothelial effects of both angiotensin-converting enzyme (ACE) inhibition and angiotensin II type 1 (AT1) receptor blockade, which have both been shown to improve endothelial function (i.e. by increasing endothelial nitric oxide availability via bradykinin-dependent endothelial nitric oxide release). ACE has a high affinity for bradykinin and degrades the peptide, so ACE inhibition may increase bradykinin-dependent effects by preventing bradykinin degradation. Interestingly, AT1-receptor blockade appears to stimulate the bradykinin-nitric oxide pathway by increased angiotensin II type 2 receptor activation. Moreover, both treatment strategies prevent increased inactivation of endothelial nitric oxide by oxygen radicals, by reducing AT1-receptor-dependent activation of the oxidant enzyme NADPH oxidase and increasing the activity of the vascular antioxidant enzyme extracellular superoxide dismutase. These beneficial effects of ACE inhibition and AT1-receptor blockade are likely to contribute to their effects on cardiovascular events.
目前已认识到内皮细胞在调节血管张力、生长、炎症反应、凝血及血小板黏附方面发挥着重要作用。内皮功能很大程度上已通过内皮依赖性血管舒张来评估，假定内皮依赖性血管运动代表其他重要内皮功能的替代标志物。采用这种方法的一个重要依据是观察到内皮依赖性血管运动和其他保护性内皮功能至少部分由一氧化氮介导。越来越多的临床研究现已证明内皮依赖性血管舒张受损与心血管事件及预后密切且独立相关。这些发现激发了人们对改善心血管高危患者内皮功能的治疗方案的兴趣。
本文描述了对血管紧张素转换酶（ACE）抑制和血管紧张素II 1型（AT1）受体阻断的内皮效应的最新见解，这两种方法均已证明可改善内皮功能（即通过缓激肽依赖性内皮一氧化氮释放增加内皮一氧化氮可用性）。ACE对缓激肽具有高亲和力并降解该肽，因此ACE抑制可能通过防止缓激肽降解来增强缓激肽依赖性效应。有趣的是，AT1受体阻断似乎通过增加血管紧张素II 2型受体激活来刺激缓激肽 - 一氧化氮途径。此外，两种治疗策略均通过减少AT1受体依赖性氧化酶NADPH氧化酶的激活并增加血管抗氧化酶细胞外超氧化物歧化酶的活性来防止内皮一氧化氮被氧自由基过度灭活。ACE抑制和AT1受体阻断的这些有益作用可能有助于它们对心血管事件的影响。
