Vascular Nitric Oxide and Oxidative Stress: Determinants of Endothelial Adaptations to Cardiovascular Disease and to Physical Activity

Abstract

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.

Nitric oxide and coronary vascular endothelium adaptations in hypertension

“…Several reports have suggested that altered NO bioavailability contributes to altered vasomotion seen in hypertension 38,47,48 and NO is the primary dilator of large epicardial coronary arteries 3,6,49 as well as a mediator of flowinduced dilation in the coronary microcirculation. 2,5,6 Given the potential importance of the NO system in the etiology of hypertensive large artery disease, and given the fact that studies in other vascular beds have revealed a number of patterns of regulation of the NO system, the importance of which is not known in the coronary bed and in hypertension, it is important to bring attention to these factors as they may be important clinically and therapeutically.…”

Exercício físico e disfunção endotelial

“…Thus, when there is an increase in shear stress, the release of NO is accelerated. In coronary circulation, this stress force also has an important role in the adaptation of the coronary flow that can increase several times during the exercises 6,19,20 .…”

“…Among the components involved in this coronary circulation improvement are: endothelial functionf. sm 9,20,57 ; the velocity of production and oxidation of NO 6,58 ; microcirculation 9,20,57,59 ; the regression of atherosclerotic lesions 3,60,61 ; the neoformation of collateral vessels 3,60,61 ; the decrease in blood viscosity 18 and the increase in the diastolic perfusion time 59 .…”

The Effect of Exercise Treadmill of Rat Liver Tissue

“…They show tissue antioxidant systems differ from each other in terms of capacity. High brain metabolic activity, oxygen consumption in excess tissues, such as liver and kidney, have a higher antioxidant capacity compared to other tissues (Fıçıcılar, Zergeroğlu, Tekin, & Ersöz, 2003;Rush, Denniss, & Graham, 2005).…”