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（通过应用程序提供）：HL-83947的总体目标是探索人类血压（BP）的交感神经调节。由于过去5年的观察结果，我们的续签应用集中在关于交感神经系统和绝经后妇女BP的新思想上。众所周知，女性的BP比成年初的男性低。但是，这种保护在更年期中消失了，此后，与年龄相似的男性相比，妇女的高血压风险加速了。沿着这些线路，我们建议绝经后妇女的BP提高“双重命中”，其中包括失去β-肾上腺素能血管舒张的损失，通常抵消年轻女性的α-肾上腺素能收缩，以及同情交感神经血管收缩活性的年龄增长。这些因素在一起导致更年期后血压的对称介导的血压升高。在这种情况下，基于此应用的主要思想是：1）在更年期血管舒张之后是ß-肾上腺素能力舒张的NO组成部分的明显减少； 2）ß-肾上腺素能血管舒张以及与年龄相关的交感神经活动的增加导致绝经后妇女对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于绝经中女性生殖激素丧失而引起的，并且可以通过更年期激素疗法（MHT）减弱； 4）也可以通过定期锻炼来减轻它们，从而可以恢复内皮功能并减少绝经后妇女的交感神经活动。 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 forward 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将测试对血压的同情支持与绝经后妇女的MSNA有关。我们将在神经节封锁之前和期间测量MSNA和动脉压。 AIM 3将测试运动训练是否增强内皮和β-肾上腺素能力舒张，并限制绝经后妇女血压的同情支持。我们还将探讨培训如何与MHT互动。重要的是，关于BP的同情和内皮控制的大多数想法对女性的底色或没有直接测试，而我们的初步数据清楚地表明了对更多数据的需求，尤其是在绝经后妇女中。由于血压控制是一个生物医学上重要的问题，因此我们提出的研究与公共卫生高度相关，还旨在提供对女性重要且知之甚少的心血管危险因素的基本机械洞察力。

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.