Characterizing Sympathetic Transduction in Humans

描述(由申请人提供)：拟议的研究将探索人类心血管控制的实质性领域的新方法，在此基础上可以建立重要的未来研究。血管交感神经流出对动脉血压的控制至关重要，无论是在每一时刻的基础上，还是在对生理应激因素的反应中。我们的目标是：1)改进交感神经活动的测量方法，使其具有高度的特异性；2)建立交感神经血管对局部血流控制的数学模型；3)推导出局部交感神经血管控制与全身动脉压控制的关系。我们将尝试通过对神经图进行显式建模并应用现代技术来提取与生理相关的信息，从而更准确地评估人类的交感神经活动。这对于提高我们了解与区域流动有关的紧张活动程度的能力至关重要。第二和第三个目标是基于这样一个事实，即交感神经活动在决定压力方面发挥着重要作用，但不是血管阻力的简单替代品。因此，我们将首先对直接测量的交感神经活动与逐跳腿部血流量的关系进行建模。交感神经活动将在生理上被驱动，以产生可重复的、离散的交感神经爆发以及不断增加的交感神经流出。随后将评估区域交感神经控制耐药性与全身压力之间的关系。自发产生的压力波将被用来探索在存在和不存在α-肾上腺素能血管收缩效应的情况下交感神经对压力控制的贡献。克服将神经活动、局部血流和全身压力控制整合到一个锐利的模型中的障碍，将为基础心血管生理学提供独特的见解，并可能在心血管病理生理学中有更广泛的应用。

DESCRIPTION (provided by applicant): The proposed research will explore new approaches to a substantive area in human cardiovascular control upon which significant future research can be built. Vascular sympathetic outflow is critical to the control of arterial pressure, both on a moment-by-moment basis and in response to physiologic stressors. Our aims are to: 1) improve the measurement of sympathetic activity so that it can be identified with a high degree of specificity, 2) mathematically model moment-by-moment sympathetic neurovascular control of regional flow, and 3) derive the relationship of regional sympathetic vascular control to systemic arterial pressure control. We will attempt to more precisely assess sympathetic activity in humans by explicitly modeling the neurogram and applying modern techniques to extract the physiologically relevant information. This is critical to enhance our capacity to appreciate the extent of nervous activity in relation to regional flow. The second and third aims are predicated on the fact that sympathetic activity plays an important role in determining pressure but is not a simple surrogate for vascular resistance. Therefore we will first model the relationship of directly measured sympathetic nerve activity to beat-by-beat leg blood flow. Sympathetic activity will be driven physiologically to produce both repeatable, discrete sympathetic bursts as well as continuously increasing sympathetic outflow. This will be followed by an assessment of the relation between regional sympathetic control of resistance and systemic pressure. Spontaneously occurring pressure waves will be exploited to probe the sympathetic contribution to pressure control in the presence and absence of alpha- adrenergic vasoconstrictor effects. Overcoming the obstacles to integrating nervous activity, regional flow, and systemic pressure control into a trenchant model will provide unique insight to basic cardiovascular physiology and may have broader application to cardiovascular pathophysiologies.