The Human Cardiovascular Control: The Role of Limb Veins

项目总结/摘要 在这个项目中，我们研究静脉扩张在血压反射调节中的作用。我们事先 在人类中的工作表明，外周肢体静脉的血管扩张引起了强大的 交感神经兴奋反射（静脉扩张反射，VDR），升高血压。在本提案中，我们有 三个具体目标：1）我们将确定花生四烯酸的环氧合酶代谢物在 唤起的VDR，并研究如何在人类中的VDR介导它们的影响。基于我们 支持试验数据，我们假设急性阻断环氧化酶系统将显著 减弱肌肉交感神经活动（MSNA）和动脉压对肢体静脉扩张的反应; 2)我们将检验肢体静脉扩张增加增益并重置操作的假设。 点的压力反射系统在健康受试者。我们推测，这些变化的增益和操作 压力反射点可以缓冲直立挑战期间的血压变化;我们还将检查 VDR和压力感受性反射之间的相互作用在男性和女性中存在差异; 3）我们将研究VDR在 在人体受试者的立位应激期间维持血压中起作用。我们假设 VDR的强度和/或VDR与压力反射之间的相互作用将与直立性相关 宽容我们还假设，“直立性高血压”的个人将有一个较高的VDR。我们 进一步推测，减少腿部静脉淤积的策略将减弱血压的升高 在这些受试者的立位挑战中。要研究的概念挑战了现行的 关于直立性压力下血压如何调节的“传统观点”。如果拟议的 目标实现后，我们将深入了解静脉扩张引起 交感神经兴奋，VDR如何与压力反射相互作用，以及这种反射如何有助于血液 在立位压力期间的压力控制。

Project Summary/Abstract In this project, we examine the role venous distention plays in the reflex regulation of blood pressure. Our prior work in humans demonstrates that vascular distension of peripheral limb veins evokes a powerful sympathoexcitatory reflex (venous distension reflex, VDR) that raises blood pressure. In this proposal, we have three specific aims: 1) we will determine the role played by cyclooxygenase metabolites of arachidonic acid in evoking the VDR, and examine how prostaglandins mediate their effects on the VDR in humans. Based on our supportive pilot data, we hypothesize that acute blockade of cyclooxygenase enzyme system will markedly attenuate muscle sympathetic nerve activity (MSNA) and arterial pressure responses to limb venous distention; 2) we will examine the hypothesis that limb venous distension increases the gain and resets the operating point of the baroreflex system in healthy subjects. We speculate that these changes in the gain and operating point of the baroreflex can buffer blood pressure changes during orthostatic challenge; We will also examine if the interaction between VDR and baroreflex differs in males and females; and 3) we will examine the role VDR plays in maintaining blood pressure during orthostatic stress in human subjects. We hypothesize that the strength of the VDR and/or the interaction between the VDR and the baroreflex will be related to orthostatic tolerance. We also hypothesize that individuals with “orthostatic hypertension” will have a heightened VDR. We further speculate that maneuvers to reduce venous pooling in legs will attenuate the increase in blood pressure during orthostatic challenge in these subjects. The concepts to be studied challenge the prevailing “conventional wisdom” regarding how blood pressure is regulated during orthostatic stress. If the proposed aims are achieved, we will gain insight into the mechanisms by which venous distension evokes sympathoexcitation, how the VDR interacts with the baroreflex, and how this reflex contributes to blood pressure control during orthostatic stress.