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Neurovascular Control and Blood Pressure Regulation in Humans

人类神经血管控制和血压调节

基本信息

批准号：
9086411
负责人：
MICHAEL J JOYNER
金额：
$ 41.51万
依托单位：
MAYO CLINIC ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-07-01 至 2018-01-15
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9086411
关键词：
Address Adrenergic Agents Age Attenuated Blood Pressure Blood flow Coupled Data Drops Endothelium Exercise Exhibits Female Forearm Goals Health Human Hypertension Hypotension Isoproterenol Laboratories Link Measures Mediating Menopause Muscle Nerve Nitric Oxide Nitric Oxide Synthase Peripheral Resistance Pharmacology Postmenopause Productivity Public Health Rest Risk Staging Sympathetic Nervous System Testing Training Trimethaphan United States National Institutes of Health Vasoconstrictor Agents Vasodilation Vasodilator Agents Woman age related artery infusion blood pressure reduction blood pressure regulation brachial artery cardiovascular risk factor constriction design emerging adult exercise training hormone therapy improved innovation insight men neurovascular novel pressure programs reproductive hormone research study response sedentary tool young man young woman

项目摘要

DESCRIPTION (provided by applicant): The overall goal of HL-83947 is to explore sympathetic regulation of blood pressure (BP) in humans. As a result of observations made over the last 5 years our renewal application is focused on novel ideas about the sympathetic nervous system and the rise in BP in postmenopausal women. It is well known that women have lower BP than men in early adulthood. However, this protection disappears at menopause, after which women have an accelerating risk of hypertension compared to men of similar age. Along these lines, we propose that there is a BP raising "double hit" in postmenopausal women that includes loss of ß-adrenergic vasodilation which normally offsets α-adrenergic constriction in young women coupled with an age related rise in sympathetic vasoconstrictor activity. Together these factors cause a sympathetically mediated rise in blood pressure after menopause. In this context, the major ideas underpinning this application are: 1) after menopause there is a marked reduction in the NO component of ß-adrenergic vasodilation; 2) this loss of ß-adrenergic vasodilation along with age related increases in sympathetic activity leads to increased sympathetic support of BP in postmenopausal women; 3) these age related changes are caused in part by a loss of female reproductive hormones at menopause and can be attenuated by Menopausal Hormone Therapy (MHT); and 4) they can also be mitigated by regular exercise which can restore endothelial function and may reduce sympathetic activity in postmenopausal women. To address these ideas we will use an ensemble of experimental tools developed and mastered in our laboratory to explore the following specific aims: Aim 1 will test whether forearm vasodilation to isoproterenol is blunted in postmenopausal women compared to young women, and whether this blunted vasodilation is due to a loss of the nitric oxide (NO) mediated component of ß-adrenergic vasodilation. Aim 2 will test whether sympathetic support of blood pressure is related to MSNA in young and postmenopausal women. We will measure MSNA and arterial pressure before and during ganglionic blockade with trimethaphan. Aim 3 will test whether exercise training augments endothelial and ß-adrenergic vasodilation and limits sympathetic support of blood pressure in postmenopausal women. We will also explore how training interacts with MHT. Importantly, most ideas about sympathetic and endothelial control of BP have undergone minimal or no direct testing in women and our preliminary data clearly show the need for more data especially in postmenopausal women. Since blood pressure control is a biomedically significant issue, the studies we propose are highly relevant to public health and also designed to provide basic mechanistic insight into an important and poorly understood cardiovascular risk factor in women.

描述（由申请方提供）：HL-83947的总体目标是探索人体血压（BP）的交感神经调节。由于过去5年的观察，我们的更新申请集中在关于交感神经系统和绝经后妇女血压升高的新想法上。众所周知，女性在成年早期的血压低于男性。然而，这种保护在更年期消失，之后女性与同龄男性相比，患高血压的风险增加。沿着这些思路，我们认为绝经后女性存在血压升高的“双重打击”，包括β-肾上腺素能血管舒张功能丧失（通常抵消年轻女性的α-肾上腺素能收缩），以及年龄相关的交感血管收缩活性升高。这些因素共同导致绝经后交感神经介导的血压升高。在这种情况下，支持这种应用的主要思想是：1）绝经后，β-肾上腺素能血管舒张的NO组分显著减少; 2）β-肾上腺素能血管舒张的这种丧失沿着与年龄相关的交感神经活性的增加，导致绝经后妇女BP的交感神经支持增加; 3）这些与年龄相关的变化部分是由绝经期女性生殖激素的损失引起的，并且可以通过月经激素治疗（MHT）来减弱;以及4）它们也可以通过定期锻炼来减轻，定期锻炼可以恢复内皮功能并且可以减少绝经后妇女的交感神经活性。为了解决这些想法，我们将使用我们实验室开发和掌握的一系列实验工具来探索以下具体目标：目标1将测试绝经后女性与年轻女性相比，异丙肾上腺素引起的前臂血管舒张是否减弱，以及这种减弱的血管舒张是否是由于一氧化氮（NO）介导的β-肾上腺素能血管舒张成分的丧失。目的2将测试血压的交感神经支持是否与年轻和绝经后妇女的MSNA有关。我们将在曲美沙芬神经节阻滞前和阻滞期间测量MSNA和动脉压。目的3将测试运动训练是否增强绝经后妇女的内皮和β-肾上腺素能血管舒张，并限制血压的交感神经支持。我们还将探讨培训如何与MHT相互作用。重要的是，大多数关于交感神经和内皮控制血压的想法在女性中进行了最小或没有直接测试，我们的初步数据清楚地表明需要更多的数据，特别是在绝经后女性中。由于血压控制是一个具有生物医学意义的问题，因此我们提出的研究与公共卫生高度相关，并且旨在为女性中一个重要且知之甚少的心血管风险因素提供基本的机制见解。

项目成果

期刊论文数量（18）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Pharmacological assessment of the contribution of the arterial baroreflex to sympathetic discharge patterns in healthy humans.

健康人动脉压力反射对交感神经放电模式贡献的药理学评估。

DOI：
10.1152/jn.00935.2017
发表时间：
2018
期刊：
Journal of neurophysiology
影响因子：
2.5
作者：
Limberg,JacquelineK;Ott,ElizabethP;Holbein,WalterW;Baker,SarahE;Curry,TimothyB;Nicholson,WayneT;Joyner,MichaelJ;Shoemaker,JKevin
通讯作者：
Shoemaker,JKevin

The relationship between muscle sympathetic nerve activity and systemic hemodynamics is altered in women with uterine fibroids.