Flavanol-Rich Cocoa, Vascular Responses and Mechanisms

富含黄烷醇的可可、血管反应和机制

• 批准号: 7583291
• 负责人: NAOMI D FISHER
• 金额: $ 46.47万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-01-01 至 2012-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7583291
• 关键词: Activities of Daily Living; Address; Adult; Affect; Age; Agreement; Area; Arginine; Atherosclerosis; Beverages; Biological Products; Blinded; Blood Circulation; Blood Flow Velocity; Blood Vessels; Blood flow; Blood specimen; Brain; Brain region; Cardiac; Cardiovascular Diseases; Cardiovascular system; Cerebrovascular Circulation; Cerebrovascular Disorders; Cerebrum; Clinical; Clinical Investigator; Cocoa Powder; Cognitive; Complement; Complex; Consumption; Coronary; Coupling; Data; Dependency; Dietary intake; Doppler Echocardiography; Elderly; Endothelium; Event; Flavanol; Flavonoids; Food; Foundations; Functional disorder; Gray unit of radiation dose; High Prevalence; Hypertension; Impaired cognition; Infusion procedures; Ingestion; Investigation; Limb structure; Magnetic Resonance Imaging; Measures; Metabolic; Methodology; Mission; NG-Nitroarginine Methyl Ester; National Center for Complementary and Alternative Medicine; National Heart, Lung, and Blood Institute; Nitric Oxide; Nitric Oxide Synthase; Perfusion; Peripheral; Physiological; Plants; Plasma; Prevention; Quality Control; Randomized Controlled Clinical Trials; Regulation; Reporting; Research; Science; Speed; Spin Labels; Tea; Techniques; Testing; Therapeutic Intervention; Time; Ultrasonography; Vasodilation; Work; cerebrovascular; drinking; frontal lobe; functional disability; gray matter; hemodynamics; improved; inhibitor/antagonist; innovation; middle cerebral artery; mimetics; neuropsychological; novel; placebo controlled study; public health relevance; red wine; response; vascular bed; white matter

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: Endothelial dysfunction is a nearly universal complement to advancing age, underlying hypertension, cardiovascular disease and frequent cognitive decline. This research examines the mechanisms by which flavanol-rich cocoa increases cerebral blood flow. Ultimately these data might lay the foundation for a trial in the prevention of cognitive decline.

描述（由申请人提供）：内皮功能障碍几乎是年龄增长的普遍现象，表现为高血压、动脉粥样硬化和心血管疾病的高患病率。衰老还与脑血流（CBF）调节的变化有关，这可能会威胁脑灌注并最终影响日常生活活动，导致功能障碍和认知受损。所有这些病症的根源在于血管受损和内皮功能障碍。潜在的纠正疗法尚不清楚。这项研究主要旨在研究富含黄烷醇的可可在两个独立循环中对血管的益处，与 NHLBI 和 NCCAM 的使命直接相关，NHLBI 的使命是研究心脑血管疾病的潜在预防和治疗方法，NCCAM 的使命是研究心脑血管疾病的潜在预防和治疗方法。在严谨的科学背景下探索植物来源的生物制剂。饮用富含类黄酮的饮料与减少冠状动脉事件有关。我们的假设归功于它们的类黄酮含量。可可含有大量黄酮类黄烷醇，可激活一氧化氮 (NO) 合酶。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。通过输注特异性 NO 合酶抑制剂 L-NAME，我们证明了该机制是 NO 依赖性的。在一项针对健康老年人的研究中，我们记录了在食用富含黄烷醇的可可两周后，通过经颅多普勒测量的脑血流量的增加。我们建议进行生理学研究来确定脑血流反应性的潜在机制以及它是否也是一氧化氮依赖性的。我们还将通过 MRI 研究脑血流，包括灰质和白质血流的区域研究和测量，预测富含黄烷醇的可可的具体增加。我们将进一步检查 MRI 和超声这两种方法，以确保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。这些试验将涉及摄入经过质量控制的富含黄烷醇的可可产品和模拟物作为对照，以及外周循环中的平行研究。 Fisher 博士将继续作为心脑血管疾病领域的独立临床研究者开展她的新工作，研究创新、有趣且广泛适用的内皮功能障碍治疗方法。旨在恢复血管内皮功能的治疗干预措施，特别是当源自天然存在的生物活性剂时，具有巨大的临床前景。 公众健康相关性：内皮功能障碍几乎是年龄增长、潜在高血压、心血管疾病和频繁认知能力下降的普遍补充。这项研究探讨了富含黄烷醇的可可增加脑血流量的机制。最终，这些数据可能为预防认知能力下降的试验奠定基础。