Dietary salt increases the risk of hypertension for some, but not all, individuals. But no method exists for assessing an individual's risk of salt-sensitive hypertension. We propose to develop an electrophysiological method of continuously monitoring the neurohormonal changes that occur after consuming salt. Our preliminary data show that the low frequency band (LFB) of heart rate variability is a promising marker for assessing salt sensitivity. The salt-sensitive group had virtually no change in LFB in response to a salt load indicating that they were unable to mount an appropriate physiological response to maintain homeostasis after consuming salt. In contrast, the salt-resistant group had a significant change in LFB but minimal increase in blood pressure (BP) after a salt load, that they were able to mount a robust physiological response which maintained appropriate BP after consuming salt. Empirical data suggests that the magnitude of the LFB change is an indicator of the strength of the body's physiological response to a salt load. ? ? Our preliminary data also demonstrate that the LFB changes are correlated with 1) the salt-induced increase in BP and 2) the activation/suppression of the neurohormonal systems involved in the maintaining salt balance. Based on the strength of these results, we propose developing a screening method which tracks LFB changes after administering an oral salt bolus. ? ? The proposed product will continuously and noninvasively measure the neurohormonal response to a salt load. Innovations include: 1) sufficient statistical power for detecting significant differences with small samples; 2) the ability to track the dynamic response to a salt load; 3) product could be cost-effectively implemented as a software modification to existing ECG instruments; 4) results are based on many cardiac cycles which greatly improves reliability; 5) completely noninvasive; 6) data is updated every 3 minutes thus facilitating the study of the kinetics of the physiological response to salt. ? ? Two protocols (oral and intravenous administration of the salt load) will be conducted to evaluate the utility of the proposed product. Three main hypotheses will be tested. First, is the LFB change correlated with the BP change in response to a salt load? Second, is the LFB measure reliable (i.e., is methods variance low)? Third, is the LFB correlated with the neurohormonal mechanisms involved in maintaining salt balance? ? ? The proposed product has significant potential for both scientific and clinical contributions. The reduced variability of the proposed product creates a powerful tool for many areas of cardiology research. With additional Phase II studies to confirm reliability and validity, the proposed product could make a significant clinical contribution by providing a rigorously tested method for assessing the individual risk of salt sensitivity, which would pave the way for realizing the promise of personal medicine: optimizing medical treatment on an individual basis. ? ? ?