Malinski Tadeusz
Department of Biochemistry, Ohio University, Athens, Ohio 45710, USA.
Am J Cardiol. 2005 Oct 10;96(7B):13i-24i. doi: 10.1016/j.amjcard.2005.07.029. Epub 2005 Aug 8.
Nitric oxide (NO) is a ubiquitous signaling molecule synthesized from L-arginine and oxygen. The process is catalyzed by NO synthase (NOS), an enzyme expressed in both constitutive (endothelial, neuronal) and inducible forms. Uncoupling of constitutive NOS leads to overproduction of superoxide (O2-) and peroxynitrite (ONOO-), 2 potent oxidants. Nanosensing techniques have been developed to monitor the physiology of NO in the beating heart in vivo. These methods involve the application of nanosensors to monitor real-time dynamics of NO production in the heart as well as the dynamics of oxidative species (oxidative stress) produced in the failing heart. Results of a recent study using nanotechnology demonstrated that African Americans have an inherent imbalance of NO, O2-, and ONOO- production in the endothelium. The overproduction of O2- and ONOO- triggers the release of aggressive radicals and damages cardiac muscle (necrosis), which may explain why African Americans are at greater risk for developing cardiovascular diseases, such as hypertension and heart failure, and are more likely to have complications than European Americans. Potential therapeutic strategies to prevent or ameliorate damage to the heart during cardiac events are prevention of O2- and ONOO- production, supplementation of NO (NO donors), and scavenging of O2- (antioxidants).
一氧化氮(NO)是一种由L-精氨酸和氧气合成的普遍存在的信号分子。该过程由一氧化氮合酶(NOS)催化,NOS以组成型(内皮型、神经型)和诱导型两种形式表达。组成型NOS的解偶联会导致超氧化物(O2-)和过氧亚硝酸根(ONOO-)这两种强效氧化剂的过量产生。已经开发出纳米传感技术来监测活体跳动心脏中NO的生理学。这些方法包括应用纳米传感器来监测心脏中NO产生的实时动态以及衰竭心脏中产生的氧化物质(氧化应激)的动态。最近一项使用纳米技术的研究结果表明,非裔美国人内皮中NO、O2-和ONOO-的产生存在内在失衡。O2-和ONOO-的过量产生会引发活性自由基的释放并损害心肌(坏死),这可能解释了为什么非裔美国人患心血管疾病(如高血压和心力衰竭)的风险更高,并且比欧洲裔美国人更容易出现并发症。预防或减轻心脏事件期间心脏损伤的潜在治疗策略包括防止O2-和ONOO-的产生、补充NO(NO供体)以及清除O2-(抗氧化剂)。