Flavanol-Rich Cocoa, Vascular Responses and Mechanisms

内皮功能障碍是一个几乎普遍的补充，以不断增长的年龄，表现为 高血压、动脉粥样硬化和心血管疾病的高患病率。老龄化也是 与脑血流量（CBF）调节的变化相关，这可能会威胁到大脑 灌注，并最终影响日常生活活动，导致功能障碍，以及 认知受损所有这些情况的基础是受损的血管， 内皮功能障碍潜在的纠正治疗尚不清楚。这项研究旨在 广泛地研究了富含黄烷醇的可可在两个独立的循环中对血管的好处， 直接关系到两个NHLBI的任务，在审查潜在的预防和 治疗心脑血管疾病，以及NCCAM，通过探索 在严格科学的背景下，植物来源的生物制剂。 富含类黄酮的饮料的消费与冠状动脉粥样硬化的减少有关。 事件;我们的假设归功于它们的类黄酮含量。可可中含有 大量的类黄酮亚类黄烷醇，显示激活一氧化氮（NO）合酶。在 在外周，我们发现可可诱导血管舒张，改善健康人的内皮功能， 人通过输注特异性NO合酶抑制剂L-NAME，我们证明， 其机制是NO依赖性的。在一项针对健康老年人的研究中，我们记录了 脑血流量--通过经颅多普勒测量--在两周富含黄烷醇的 可可。我们建议进行生理研究来确定脑血的机制 血流反应性以及它是否也是NO依赖性的。我们还将研究脑血流 通过MRI，包括区域研究和灰色和白色物质的流动测量， 特别是富含黄烷醇的可可。我们将进一步研究这两种方法，MRI 和超声波，用于测量脑血流量的一致性。功能性TCD反应 将评估神经血管耦合的潜在增强。试验将涉及摄入 质量受控的富含黄烷醇的可可产品和作为对照的模拟物，以及平行的 外周循环的研究。 费舍尔博士将继续她的新工作，作为一个独立的临床研究者在该地区的 心血管疾病，研究内皮功能障碍的治疗， 创新，有趣和广泛适用。旨在恢复 血管内皮功能，特别是当来自天然存在的生物学 活性剂，具有巨大的临床前景。

Endothelial dysfunction is a nearly universal complement to advancing age, manifest by a high prevalence of hypertension, atherosclerosis, and cardiovascular disease. Aging is also associated with changes in cerebral blood flow (CBF) regulation which may threaten cerebral perfusion and ultimately affect activities of daily living, resulting in functional disabilities as well as impaired cognition. Underlying all of these conditions lies the damaged blood vessel with a dysfunctional endothelium. Potential corrective therapies are unknown. This research, aimed broadly at studying the vascular benefits of flavanol-rich cocoa in two separate circulations, is directly related to the missions of both the NHLBI, in examining a potential prevention and treatment for cardiac and cerebrovascular disease, and of the NCCAM, by exploring a botanically-derived biological agent in the context of rigorous science. Consumption of flavonoid-rich beverages has been associated with a reduction in coronary events; our hypothesis credits their flavonoid content. Cocoa can contain extraordinary amounts of the flavonoid subset flavanols, shown to activate nitric oxide (NO) synthase. In the periphery, we showed that cocoa induced vasodilation, improving endothelial function in healthy people. Through infusion of the specific NO synthase inhibitor L-NAME, we demonstrated that the mechanism is NO- dependent. In a study of healthy elderly, we documented a rise in cerebral blood flow -- measured by transcranial Doppler -- following two weeks of flavanol-rich cocoa. We propose physiologic studies to determine the mechanism underlying cerebral blood flow responsiveness and whether it, too, is NO- dependent. We will also study brain blood flow by MRI, including regional studies and measures of flow in gray and white matter, anticipating specific increases with flavanol-rich cocoa. We will further examine the two methodologies, MRI and ultrasound, for concordance in measuring cerebral blood flow. Functional TCD responses will assess potential enhancement of neurovascular coupling. The trials will involve ingestion of a quality-controlled flavanol-rich cocoa product and mimetic as control, as well as parallel studies in the peripheral circulation. Dr. Fisher will continue her novel work as an independent clinical investigator in the area of cardio- and cerebrovascular disease, studying treatments of endothelial dysfunction that are innovative, intriguing and broadly applicable. Therapeutic interventions aimed at restoring vascular endothelial function, especially when derived from a naturally occurring biologically active agent, hold tremendous clinical promise.