Neurovascular Control and Blood Pressure Regulation in Humans

人类神经血管控制和血压调节

• 批准号: 8879184
• 负责人: MICHAEL J JOYNER
• 金额: $ 40.88万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8879184
• 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; Training Programs; Trimethaphan; United States National Institutes of Health; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents; Woman; adrenergic; age related; artery infusion; blood pressure reduction; blood pressure regulation; brachial artery; cardiovascular risk factor; constriction; design; emerging adult; hormone therapy; improved; innovation; insight; men; novel; pressure; reproductive hormone; research study; response; sedentary; tool; young man; young woman

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（由申请人提供）：HL-83947的总体目标是探索人类血压（BP）的交感调节。根据过去5年的观察结果，我们的更新申请集中在交感神经系统和绝经后妇女血压升高的新观点上。众所周知，在成年早期，女性的血压比男性低。然而，这种保护在绝经后就消失了，绝经后女性患高血压的风险比同龄男性要高。沿着这些线，我们提出绝经后妇女存在血压升高的“双重打击”，包括ß-肾上腺素能血管舒张的丧失（通常抵消年轻妇女的α-肾上腺素能收缩），以及交感血管收缩活性的年龄相关上升。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，支持这一应用的主要思想是：1)绝经后ß-肾上腺素能血管舒张的NO成分显着减少；2) ß-肾上腺素能血管舒张功能的丧失以及交感神经活动的年龄相关增加导致绝经后妇女交感神经支持血压增加；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丧失引起的，可通过绝经期激素治疗（MHT）减轻；4)它们也可以通过定期运动来缓解这可以恢复内皮功能并可能减少绝经后妇女的交感神经活动。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：目的1将测试绝经后妇女对异丙肾上腺素的前臂血管舒张是否与年轻女性相比变得迟钝，以及这种迟钝的血管舒张是否由于一氧化氮（NO）介导的ß-肾上腺素能血管舒张成分的损失。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。我们将在使用三甲沙芬阻断神经节之前和期间测量MSNA和动脉压。目的3将测试运动训练是否增强内皮和ß-肾上腺素能血管舒张，并限制绝经后妇女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细胞控制血压的观点在女性中进行了很少或没有直接测试，我们的初步数据清楚地表明需要更多的数据，特别是绝经后妇女。由于血压控制是一个重要的生物医学问题，我们提出的研究与公共卫生高度相关，也旨在为女性心血管危险因素提供基本的机制见解。