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.