Vascular Biology and Immunopharmacology Group, Department of Pharmacology, Monash University, Wellington Rd, Clayton, Victoria 3800, Australia.
Front Biosci (Landmark Ed). 2011 Jan 1;16(5):1733-45. doi: 10.2741/3816.
Maintenance of vascular tone by the endothelium involves the production of endothelium-derived nitric oxide (NO). NO, produced from endothelial nitric oxide synthase diffuses to the underlying smooth muscle to stimulate soluble guanylate cyclase, resulting in increased cyclic GMP levels, and subsequent smooth muscle relaxation and blood vessel dilatation. Endothelial dysfunction, manifested as diminished NO bioavailability, is a common feature of a number of vascular-related diseases.. Oxidative stress can be defined as an imbalance between reactive oxygen species (ROS) production and/or impaired ROS metabolism that favours them being present in excess of physiological levels. Oxidative stress can negatively impact many cell types, including in the vasculature. There is now a wealth of evidence suggesting that oxidative stress is a major cause of endothelial dysfunction in the cerebral circulation. This review will summarize disease models in which both oxidative stress and endothelial dysfunction occur in the cerebral circulation, namely hypertension involving angiotensin II (Ang II), diabetes, subarachnoid hemorrhage, stroke and Alzheimer's disease. Molecular mechanisms by which oxidative stress occurs, (eg increased NADPH-oxidase activity) will also be discussed.
血管张力的维持依赖于内皮细胞产生的内皮衍生的一氧化氮（NO）。NO 由内皮型一氧化氮合酶产生，扩散到平滑肌下层，刺激可溶性鸟苷酸环化酶，导致环鸟苷酸水平升高，随后平滑肌松弛和血管扩张。内皮功能障碍表现为一氧化氮生物利用度降低，是多种血管相关疾病的共同特征。氧化应激可定义为活性氧（ROS）产生和/或 ROS 代谢受损之间的失衡，导致 ROS 过量存在于生理水平之上。氧化应激会对包括血管在内的多种细胞类型产生负面影响。现在有大量证据表明，氧化应激是脑循环中内皮功能障碍的主要原因。这篇综述将总结脑循环中同时存在氧化应激和内皮功能障碍的疾病模型，即涉及血管紧张素 II（Ang II）的高血压、糖尿病、蛛网膜下腔出血、中风和阿尔茨海默病。还将讨论氧化应激发生的分子机制（例如 NADPH 氧化酶活性增加）。
