Flavanol-Rich Cocoa, Vascular Responses and Mechanisms

内皮功能障碍几乎是增龄的普遍补充，表现为 高血压、动脉粥样硬化和心血管疾病的高发。老龄化也是 与脑血流(CBF)调节的变化相关，这可能威胁到大脑 灌流并最终影响日常生活活动，导致功能障碍 认知功能受损。在所有这些情况下，受损的血管都有 内皮功能失调。潜在的矫正疗法尚不清楚。这项研究旨在 广泛地研究富含黄烷醇的可可在两个不同的循环中对血管的好处，是 直接与NHLBI的任务有关，在审查潜在的预防和 心脑血管疾病的治疗，以及NCCAM，通过探索一种 在严谨科学的背景下植物衍生的生物制剂。 饮用富含类黄酮的饮料与冠状动脉病变的减少有关 我们的假设归功于它们的类黄酮类含量。可可可以含有非同寻常的 数量的黄酮亚组黄烷醇，显示激活一氧化氮合酶(NO)。在 外围，我们发现可可诱导血管扩张，改善健康人的内皮功能 人民。通过输注特异性一氧化氮合酶抑制剂L-NAME，我们证明了 这种机制是不依赖的。在一项对健康老年人的研究中，我们记录了 富含黄烷醇的两周后经颅多普勒测量脑血流量 可可。我们建议进行生理学研究，以确定脑血流的机制。 流动的响应性，以及它是否也是不依赖的。我们还将研究脑血流 通过磁共振成像，包括区域研究和灰质和白质血流的测量，预测 与富含黄烷醇的可可一起增加。我们将进一步研究这两种方法，核磁共振 以及超声波，用于测量脑血流量的一致性。功能性经颅多普勒反应 将评估神经血管偶联的潜在增强。试验将涉及摄取 一种质量受控的富含黄烷醇的可可产品，以仿制为对照，以及平行 外周循环方面的研究。 Fisher博士将继续她作为一名独立临床调查员在以下领域的新工作 心脑血管疾病，研究内皮功能障碍的治疗 创新、耐人寻味、适用范围广。旨在恢复 血管内皮细胞功能，尤其是来自自然发生的生物学上的血管内皮功能 活性物质，具有巨大的临床应用前景。

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.