Rush James W E, Denniss Steven G, Graham Drew A
Department of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada.
Can J Appl Physiol. 2005 Aug;30(4):442-74. doi: 10.1139/h05-133.
Cardiovascular disease is the single leading cause of death and morbidity for Canadians. A universal feature of cardiovascular disease is dysfunction of the vascular endothelium, thus disrupting control of vasodilation, tissue perfusion, hemostasis, and thrombosis. Nitric oxide bioavailability, crucial for maintaining vascular endothelial health and function, depends on the processes controlling synthesis and destruction of nitric oxide as well as on the sensitivity of target tissue to nitric oxide. Evidence supports a major contribution by oxidative stress-induced destruction of nitric oxide to the endothelial dysfunction that accompanies a number of cardiovascular disease states including hypertension, diabetes, chronic heart failure, and atherosclerosis. Regular physical activity (exercise training) reduces cardiovascular disease risk. Numerous studies support the hypothesis that exercise training improves vascular endothelial function, especially when it has been impaired by preexisting risk factors. Evidence is emerging to support a role for improved nitric oxide bioavailability with training as a result of enhanced synthesis and reduced oxidative stress-mediated destruction. Molecular targets sensitive to the exercise training effect include the endothelial nitric oxide synthase and the antioxidant enzyme superoxide dismutase. However, many fundamental details of the cellular and molecular mechanisms linking exercise to altered molecular and functional endothelial phenotypes have yet to be discovered. The working hypothesis is that some of the cellular mechanisms contributing to endothelial dysfunction in cardiovascular disease can be targeted and reversed by signals associated with regular increases in physical activity. The capacity for exercise training to regulate vascular endothelial function, nitric oxide bioavailability, and oxidative stress is an example of how lifestyle can complement medicine and pharmacology in the prevention and management of cardiovascular disease.
心血管疾病是加拿大单一的首要死亡和发病原因。心血管疾病的一个普遍特征是血管内皮功能障碍，从而破坏对血管舒张、组织灌注、止血和血栓形成的控制。一氧化氮生物利用度对于维持血管内皮健康和功能至关重要，它取决于控制一氧化氮合成和破坏的过程以及靶组织对一氧化氮的敏感性。有证据表明，氧化应激诱导的一氧化氮破坏对包括高血压、糖尿病、慢性心力衰竭和动脉粥样硬化在内的多种心血管疾病状态所伴随的内皮功能障碍有重大影响。规律的体育活动（运动训练）可降低心血管疾病风险。大量研究支持这样的假说，即运动训练可改善血管内皮功能，尤其是当它因先前存在的危险因素而受损时。越来越多的证据支持运动训练可通过增强合成和减少氧化应激介导的破坏来提高一氧化氮生物利用度。对运动训练效果敏感的分子靶点包括内皮型一氧化氮合酶和抗氧化酶超氧化物歧化酶。然而，将运动与改变的分子和功能性内皮表型联系起来的细胞和分子机制的许多基本细节尚未被发现。目前的工作假说是，心血管疾病中导致内皮功能障碍的一些细胞机制可以通过与规律的体力活动增加相关的信号来靶向和逆转。运动训练调节血管内皮功能、一氧化氮生物利用度和氧化应激的能力是生活方式如何在心血管疾病的预防和管理中补充医学和药理学的一个例子。
