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对年龄的普遍补充，这表现为高血压，动脉粥样硬化和心血管疾病的高流行。衰老还与大脑血流（CBF）调节的变化有关，这可能威胁到脑灌注并最终影响日常生活的活动，从而导致功能障碍以及认知受损。所有这些疾病的基础都处于受损的血管，内皮功能障碍。潜在的纠正疗法未知。这项研究旨在在两个单独的循环中研究富含黄白醇的可可醇的血管益处，直接与NHLBI的任务直接相关，以检查通过植物学生物学的严格科学探索，检查了对心脏和脑血管疾病的潜在预防和治疗，以及NCCAM的潜在预防和治疗。消费富含类黄酮的饮料与冠状动脉事件的减少有关。我们的假设将其类黄酮含量归功于。可可可以包含非凡量的类黄酮亚群黄酮，可激活一氧化氮（NO）合酶。在外围，我们表明可可诱导的血管舒张，改善健康人的内皮功能。通过输注特定的NO合酶抑制剂L名称，我们证明了该机制是不依赖的。在一项健康的老年人的研究中，我们记录了脑血流的升高 - 通过经颅多普勒测量 - 在富含黄酮醇的可可之后。我们提出生理研究，以确定脑血流反应能力的基础机制，以及它也不取决于它。我们还将通过MRI研究脑血流，包括区域研究和灰色和白质流量的度量，预测富含黄酮醇的可可的特异性增加。我们将进一步研究MRI和超声检查的两种方法，以在测量脑血流中进行一致性。功能性TCD响应将评估神经血管耦合的潜在增强。这些试验将涉及摄入富含黄烷醇的可可产物和模拟对照的质量控制，以及在外围循环中的平行研究。费舍尔博士将继续她作为心脏和脑血管疾病领域的独立临床研究者的新工作，研究内皮功能障碍的治疗方法，这些治疗是创新，有趣且广泛适用的。旨在恢复血管内皮功能的治疗干预措施，尤其是在天然存在的生物学活性剂中衍生出来的临床前景。 公共卫生相关性：内皮功能障碍几乎是对促进年龄，潜在的高血压，心血管疾病和频繁认知能力下降的普遍补充。这项研究研究了富含黄酮醇的可可增加脑血流的机制。最终，这些数据可能为预防认知能力下降的试验奠定了基础。