Exercise, Histamine Receptors, & Vascular Health In Aging

运动、组胺受体、

基本信息

批准号：
9062492
负责人：
John R. Halliwill
金额：
$ 39.84万
依托单位：
UNIVERSITY OF OREGON
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-06-05 至 2019-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9062492
关键词：
Acute Address Age Aging Anaphylaxis Asthma Blood Vessels Blood flow CCL2 gene Cardiovascular Diseases Cell Culture Techniques Cell Line Cell physiology Cells Data Documentation Endothelial Cells Exercise Future Gene Proteins Goals Health Health Benefit Histamine Histamine H2 Receptors Histamine Production Histamine Receptor Histamine Release Human Hypersensitivity Hypertension Individual Intervention Intervention Studies Knowledge Link Mediating Modality Muscle Oxidative Stress Pathway interactions Patients Peripheral Peripheral arterial disease Personal Satisfaction Physical activity Play Population Prevention Production Reactive Oxygen Species Receptor Activation Regional Blood Flow Regulation Risk Factors Role Signal Transduction Signaling Molecule Skeletal Muscle Source Staging Stimulus System Techniques Testing Therapeutic Time Up-Regulation Vascular Diseases Vascular Endothelial Growth Factors Vascular remodeling Vasodilation Work aged cardiovascular disorder prevention cardiovascular health cohort design endothelial dysfunction exercise training improved mast cell novel older men older women response tumor growth

项目摘要

DESCRIPTION (provided by applicant): Vascular health declines with aging, and the decline is associated with peripheral artery disease. The long- term goal of this proposal is to understand the link between exercise, histamine receptors, and alterations in endothelial and vascular function so that we can exploit this link to generate novel interventions to improve or maintain vascular health in aging and treat patients with peripheral artery disease. In this context, a single bout of exercise is followed by a sustained peripheral vasodilation of the previously active skeletal muscle ("sustained post exercise vasodilation"). Histamine H1 and H2-receptors are the primary cause of sustained post exercise vasodilation. We speculate that this histaminergic pathway may play a role in improving endothelial function and stimulating vascular remodeling in response to exercise. It is unknown what signals associated with exercise activate this histaminergic pathway, or whether histamine released from mast cells or de novo production of histamine is responsible for activation of H1 and H2-receptors following exercise. It is unknown what signals related to endothelial function and vascular remodeling are dependent on activation of these receptors. Lastly, it is unclear whether the histaminergic pathway remains responsive to exercise or other stimuli in older subjects. We propose the following specific aims: 1) Identify the exercise-related signal that activates this histaminergic pathway, 2) Determine the source of histamine released by this signal, 3) Determine key endothelial and vascular regulatory signals that respond to activation of this pathway, and 4) Determine responsiveness of this pathway to exercise in older men and women. These aims are supported by the PI's prior work and will be addressed using state-of-the-art techniques in humans. Information from these studies will prove valuable on five fronts. First, these studies will expand current understanding of the vascular changes that occur following exercise. Second, we expect these studies will prove that histamine, generally associated with pathophysiological responses (e.g., asthma, allergies, anaphylaxis, and tumor growth), can play important roles in day-to-day regulation of regional blood flow related to exercise. Third, we expect these studies will identify a key pathway that contributes to the cardiovascular health benefits of lifetime physical activity by modulating critical signals for endothelial and vascular health. Fourth, we expect to show this pathway is functional in older men and women. Last, we expect these studies will identify a mechanism that can be exploited by future interventions to protect the vasculature from the age-associated decline in endothelial and vascular health and to treat peripheral artery disease. In summary, these studies will contribute to the understanding of exercise as a therapeutic modality in treatment and prevention of cardiovascular disease and set the stage for new vascular health interventions targeted at older individuals, in particular, those with conditions such as peripheral artery disease.

描述（由申请人提供）：血管健康随着年龄的增长而下降，并且这种下降与外周动脉疾病有关。该提案的长期目标是了解运动、组胺受体以及内皮和血管功能改变之间的联系，以便我们可以利用这种联系来制定新的干预措施，以改善或维持衰老过程中的血管健康，并治疗外周血管疾病患者。动脉疾病。在这种情况下，单次运动后，先前活跃的骨骼肌会持续外周血管舒张（“持续运动后血管舒张”）。组胺 H1 和 H2 受体是运动后血管持续舒张的主要原因。我们推测这种组胺能途径可能在改善内皮功能和刺激运动响应的血管重塑中发挥作用。目前尚不清楚与运动相关的哪些信号会激活这种组胺能通路，也不知道肥大细胞释放的组胺或组胺的从头产生是否负责运动后 H1 和 H2 受体的激活。目前尚不清楚与内皮功能和血管重塑相关的哪些信号依赖于这些受体的激活。最后，尚不清楚老年受试者的组胺能通路是否仍然对运动或其他刺激有反应。我们提出以下具体目标：1) 识别激活该组胺能通路的运动相关信号，2) 确定该信号释放的组胺来源，3) 确定响应该通路激活的关键内皮和血管调节信号， 4) 确定老年男性和女性该途径对运动的反应。这些目标得到了 PI 之前工作的支持，并将通过人类最先进的技术来实现。这些研究的信息将在五个方面被证明是有价值的。首先，这些研究将扩大目前对运动后发生的血管变化的理解。其次，我们期望这些研究将证明，组胺通常与病理生理反应（例如哮喘、过敏、过敏反应和肿瘤生长）相关，可以在与运动相关的局部血流的日常调节中发挥重要作用。第三，我们预计这些研究将确定一条关键途径，通过调节内皮和血管健康的关键信号，促进终生体力活动对心血管健康的益处。第四，我们希望证明这一途径在老年男性和女性中是有效的。最后，我们预计这些研究将确定一种机制，未来的干预措施可以利用该机制来保护脉管系统免受与年龄相关的内皮和血管健康下降的影响，并治疗外周动脉疾病。总之，这些研究将有助于理解运动作为治疗和预防心血管疾病的一种治疗方式，并为针对老年人，特别是患有外周动脉疾病等疾病的老年人的新血管健康干预措施奠定基础。

项目成果

期刊论文数量（17）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Differential Post-Exercise Blood Pressure Responses between Blacks and Caucasians.

DOI：
10.1371/journal.pone.0153445
发表时间：
2016
期刊：
PloS one
影响因子：
3.7
作者：
Yan H;Behun MA;Cook MD;Ranadive SM;Lane-Cordova AD;Kappus RM;Woods JA;Wilund KR;Baynard T;Halliwill JR;Fernhall B
通讯作者：
Fernhall B

Neurovascular control following small muscle-mass exercise in humans.

人类小肌肉运动后的神经血管控制。

DOI：
10.14814/phy2.12289
发表时间：
2015
期刊：
Physiological reports
影响因子：
2.5
作者：
Buck,TahishaM;Romero,StevenA;Ely,MatthewR;Sieck,DylanC;Abdala,PedroM;Halliwill,JohnR
通讯作者：
Halliwill,JohnR

Thin-beam ultrasound overestimation of blood flow: how wide is your beam?