Rudic R D, Shesely E G, Maeda N, Smithies O, Segal S S, Sessa W C
Department of Pharmacology, Yale University School of Medicine, Boyer Center for Molecular Medicine, New Haven, Connecticut 06536, USA.
J Clin Invest. 1998 Feb 15;101(4):731-6. doi: 10.1172/JCI1699.
The vascular endothelium mediates the ability of blood vessels to alter their architecture in response to hemodynamic changes; however, the specific endothelial-derived factors that are responsible for vascular remodeling are poorly understood. Here we show that endothelial-derived nitric oxide (NO) is a major endothelial-derived mediator controlling vascular remodeling. In response to external carotid artery ligation, mice with targeted disruption of the endothelial nitric oxide synthase gene (eNOS) did not remodel their ipsilateral common carotid arteries whereas wild-type mice did. Rather, the eNOS mutant mice displayed a paradoxical increase in wall thickness accompanied by a hyperplastic response of the arterial wall. These findings demonstrate a critical role for endogenous NO as a negative regulator of vascular smooth muscle proliferation in response to a remodeling stimulus. Furthermore, our data suggests that a primary defect in the NOS/NO pathway can promote abnormal remodeling and may facilitate pathological changes in vessel wall morphology associated with complex diseases such as hypertension and atherosclerosis.
血管内皮介导血管响应血流动力学变化而改变其结构的能力；然而，负责血管重塑的特定内皮衍生因子却知之甚少。在此我们表明，内皮衍生的一氧化氮（NO）是控制血管重塑的主要内皮衍生介质。响应颈外动脉结扎，内皮型一氧化氮合酶基因（eNOS）靶向缺失的小鼠未对其同侧颈总动脉进行重塑，而野生型小鼠则进行了重塑。相反，eNOS突变小鼠的管壁厚度出现反常增加，并伴有动脉壁的增生反应。这些发现证明内源性NO作为响应重塑刺激的血管平滑肌增殖的负调节因子具有关键作用。此外，我们的数据表明，NOS/NO途径中的原发性缺陷可促进异常重塑，并可能促进与高血压和动脉粥样硬化等复杂疾病相关的血管壁形态的病理变化。
