Ferrari R, Bachetti T, Agnoletti L, Comini L, Curello S
Chair of Cardiology, University of Brescia, Italy.
Eur Heart J. 1998 Jul;19 Suppl G:G41-7.
The endothelium controls vascular smooth muscle tone by secreting substances that cause relaxation and contraction. Under physiological, basal conditions the endothelium constantly releases nitric oxide, a process closely regulated by the effect of shear stress on endothelial cells. Recent data raise the possibility that, among many other substances, bradykinin also plays an important role in the regulation of vascular tone. Bradykinin is a vasodilator that increases the activity of constitutive nitric oxide. Congestive heart failure (CHF) is a complex clinical syndrome in which abnormal vascular endothelial function has been shown to occur at both the experimental and clinical level. The reduced nitric oxide-mediated vasodilation in CHF is multifactorial. Constitutive nitric oxide synthase is downregulated as shear stress is reduced. Vascular angiotensin-converting enzyme (ACE), which produces angiotensin II and inactivates bradykinin, is up-regulated. Angiotensin II is a powerful vasoconstrictor, and the reduced availability of bradykinin will further down-regulate constitutive nitric oxide synthase. The CHF-induced activation of tumour necrosis factor also leads to a down-regulation of constitutive nitric oxide synthase and to an increased rate of endothelial-cell apoptosis. These observations suggest that abnormalities of endothelial function in CHF may contribute to increased peripheral vasomotor tone both at rest and during exercise, and raise the possibility that the beneficial effects of ACE inhibition in CHF may be due in part to improved endothelial function.
内皮细胞通过分泌引起舒张和收缩的物质来控制血管平滑肌张力。在生理基础条件下，内皮细胞持续释放一氧化氮，这一过程受剪切应力对内皮细胞作用的严格调控。最近的数据表明，在许多其他物质中，缓激肽在血管张力调节中也起着重要作用。缓激肽是一种血管舒张剂，可增加内源性一氧化氮的活性。充血性心力衰竭（CHF）是一种复杂的临床综合征，在实验和临床水平上均已显示存在异常的血管内皮功能。CHF中一氧化氮介导的血管舒张功能降低是多因素的。随着剪切应力降低，内源性一氧化氮合酶下调。产生血管紧张素II并使缓激肽失活的血管紧张素转换酶（ACE）上调。血管紧张素II是一种强大的血管收缩剂，缓激肽可用性降低会进一步下调内源性一氧化氮合酶。CHF诱导的肿瘤坏死因子激活也导致内源性一氧化氮合酶下调和内皮细胞凋亡率增加。这些观察结果表明，CHF中内皮功能异常可能导致静息和运动时外周血管运动张力增加，并增加了ACE抑制在CHF中的有益作用可能部分归因于内皮功能改善的可能性。
