Miller Alyson A, Drummond Grant R, Sobey Christopher G
Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.
Pharmacol Ther. 2006 Sep;111(3):928-48. doi: 10.1016/j.pharmthera.2006.02.005. Epub 2006 Apr 17.
Reactive oxygen species (ROS) are thought to play an important role in the initiation and progression of a variety of vascular diseases. Furthermore, accumulating evidence indicates that ROS may also serve as important cell signalling molecules for the regulation of normal vascular function. Recently, a novel family of proteins (Nox1, 2 and 4) that act as the catalytic subunit of the superoxide (O2-) producing enzyme NADPH-oxidase has been discovered in vascular cells. There is now preliminary evidence suggesting that NADPH-oxidase-derived ROS may serve as a physiological vasodilator mechanism in the cerebral circulation. Moreover, the activity of NADPH-oxidase is profoundly greater in cerebral versus systemic arteries. Studies have shown that Nox1, Nox2 (also known as gp91phox) and Nox4 are all expressed in cerebral arteries, suggesting that multiple isoforms of NADPH-oxidase may be important for ROS production by cerebral arteries. Enhanced NADPH-oxidase activity is associated with several vascular-related diseases, including hypertension, stroke, subarachnoid haemorrhage and Alzheimer's dementia; however, the consequences of this for cerebral vascular function are controversial. For example, there is some evidence suggesting that NADPH-oxidase-derived O2- may play a role in endothelial dysfunction of cerebral arteries and a subsequent rise in cerebral vascular tone, associated with hypertension. However, activation of NADPH-oxidase elicits cerebral vasodilatation in vivo, and this mechanism is enhanced in chronic hypertension. While further supportive evidence is needed, it is an intriguing possibility that NADPH-oxidase-derived ROS may play a protective role in regulating cerebral vascular tone during disease.
活性氧（ROS）被认为在多种血管疾病的发生和发展中起重要作用。此外，越来越多的证据表明，ROS也可能作为调节正常血管功能的重要细胞信号分子。最近，在血管细胞中发现了一类新的蛋白质家族（Nox1、2和4），它们作为产生超氧化物（O2-）的酶NADPH氧化酶的催化亚基。现在有初步证据表明，NADPH氧化酶衍生的ROS可能作为脑循环中的一种生理性血管舒张机制。此外，与全身动脉相比，脑动脉中NADPH氧化酶的活性明显更高。研究表明，Nox1、Nox2（也称为gp91phox）和Nox4在脑动脉中均有表达，这表明NADPH氧化酶的多种同工型可能对脑动脉产生ROS很重要。NADPH氧化酶活性增强与包括高血压、中风、蛛网膜下腔出血和阿尔茨海默病痴呆在内的几种血管相关疾病有关；然而，这对脑血管功能的影响存在争议。例如，有一些证据表明，NADPH氧化酶衍生的O2-可能在脑动脉内皮功能障碍以及随后与高血压相关的脑血管张力升高中起作用。然而，NADPH氧化酶的激活在体内会引起脑血管舒张，并且这种机制在慢性高血压中会增强。虽然还需要进一步的支持性证据，但NADPH氧化酶衍生的ROS在疾病期间调节脑血管张力方面可能发挥保护作用，这是一个有趣的可能性。
