Neurovascular Control and Blood Pressure Regulation in Humans

人类神经血管控制和血压调节

• 批准号: 8307651
• 负责人: MICHAEL J JOYNER
• 金额: $ 4.76万
• 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 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8307651
• 关键词: Address; Adrenergic Agents; Adrenergic Receptor; Aging; Baroreflex; Blood Pressure; Blood Vessels; Blood Volume; Cardiac Output; Equilibrium; Genomics; Hour; Human; Hypertension; Individual; Link; Low Cardiac Output; Lower Body Negative Pressure; Measurement; Nerve; Pathway interactions; Research Personnel; Staging; Stimulus; Testing; Variant; Vasoconstrictor Agents; Woman; adrenergic; blood pressure regulation; insight; male; men; normal aging; normotensive; older men; older women; pressure; programs; receptor

DESCRIPTION (provided by applicant): This proposal explores the balance between sympathetic vasoconstrictor activity and blood pressure regulation in younger and older humans. While baseline sympathetic nerve activity (MSNA) is stable in young normotensive males, there is wide inter-individual variation in baseline MSNA and no clear relationship between MSNA and arterial pressure. Additionally, sympathetic activity increases with normal aging but is not consistently associated with marked increases in arterial pressure. In this context, our recent studies suggest a balance among sympathetic activity, cardiac output, and vasoconstrictor responsiveness to adrenergic stimuli might explain how arterial pressure remains normal when baseline sympathetic activity is high. By exploring the following specific aims we test the overall hypotheses that high baseline sympathetic activity in normotensive younger and older subjects is balanced by reciprocal changes in cardiac output and vascular adrenergic responsiveness that limit the blood pressure raising impact of the sympathoexcitation. Specific Aim 1: We will test whether the reciprocal relationship between cardiac output (CO) and sympathetic nerve activity is disrupted by normal aging. We hypothesize that this relationship is not disrupted but that healthy older subjects have lower cardiac outputs and proportionally higher sympathetic activity than young subjects. Our secondary hypothesis is that women have a similar CO-MSNA relationship to men, but for any given CO, sympathetic activity is lower in women. A tertiary hypothesis is that baseline MSNA will not be related to 24 hour ambulatory blood pressure measurements. Specific Aim 2: We will test whether changes in blood volume and CO with normal aging are linked to the increase in MSNA by using volume expansion and lower body negative pressure to manipulate CO. We hypothesize that sympathetic activity will be similar at a given CO and arterial pressure in both older and younger subjects. Specific Aim 3: We will test whether a1- versus a2-adrenergic receptors are involved in the decreased vascular responsiveness seen in normotensive subjects with high MSNA. We hypothesize there will be an inverse relationship between baseline MSNA and vascular responsiveness that will be most obvious for a1-receptors in both younger and older subjects. We also propose exploratory analysis of genomic variation in a1- and a2-adrenergic receptors and related pathways from subjects with varying levels of baseline sympathetic activity. Specific Aim 4: We will test whether baroreflex control of MSNA is related to baseline MSNA and how this changes with aging. We hypothesize that subjects with high baseline MSNA will demonstrate blunted baroreflex control of MNSA. In summary, this overall approach will permit us to understand how normotensive is maintained in humans with high baseline sympathetic activity and set the stage for understanding how these mechanisms might fail in hypertension.

描述（由申请人提供）：该提案探讨了年轻人和年龄较大人类的交感神经活动和血压调节之间的平衡。虽然基线交感神经活性（MSNA）在年轻的正常雄性男性中稳定，但基线MSNA的个体间差异很大，MSNA与动脉压之间没有明显的关系。另外，交感神经活动随正常衰老而增加，但与动脉压的明显增加不一致。在这种情况下，我们最近的研究表明，当基线交感神经活动较高时，对肾上腺能刺激的交感神经活动，心脏输出和血管收缩反应能力之间的平衡可能会如何保持正常。通过探索以下特定目的，我们测试了总体假设，即在心脏输出和血管肾上腺素能反应的相互变化中，平衡了正常的年轻和年龄较大受试者的高基线交感神经活动，从而限制了交感神经激发的血压升高影响。具体目标1：我们将测试心输出（CO）和交感神经活动之间的相互关系是否因正常衰老而破坏。我们假设这种关系并没有被破坏，但是健康的老年受试者的心输出量较低，并且比年轻受试者相比具有更高的交感神经活动。我们的次要假设是女性与男性具有相似的共同关系，但是对于任何给定的CO，女性的同情活动都较低。第三个假设是基线MSNA与24小时的卧床血压测量无关。具体目标2：我们将测试通过使用体积膨胀和操纵CO的下体负压的血量变化与MSNA的增加与MSNA的增加有关。我们假设在给定的CO和老年人和年轻受试者中，在给定的CO和动脉压力下，交感神经活动将相似。具体目标3：我们将测试A1-与A2肾上腺素能受体是否参与高MSNA正常受试者的血管反应性降低。我们假设基线MSNA和血管反应性之间将存在反比关系，这对于年轻受试者和年龄较大受试者中的A1受体最为明显。我们还提出了对基线交感神经水平不同的受试者的A1和A2-肾上腺素能受体以及相关途径的基因组变异的探索性分析。特定目标4：我们将测试MSNA的压力反射控制是否与基线MSNA有关，以及与衰老的变化如何变化。我们假设具有高基线MSNA的受试者将证明MNSA的压力反射控制钝。总而言之，这种总体方法将使我们能够理解具有高基线交感神经活动的人类如何保持正常的兴趣，并为了解这些机制如何在高血压中失败奠定了基础。