application) Salt sensitivity is a poorly defined phenotype, characterized by the effect of high/low salt intake on blood pressure. The main objective of this project is to characterize cellular phenotypes of salt sensitivity based on the cellular Ca2+ responses to altered sodium intake. The central hypothesis is that, at the cellular level, salt sensitivity entails an accelerated external Ca2+ entry through store operated Ca2+ channels (SOCC) in concert with an accelerated cellular Ca2+ extrusion through the Na+/Ca2+ exchanger, i.e., an accelerated cellular Ca2+ turnover rate. In and of itself, this cellular phenotype increases neither the cellular Ca2+ load nor the blood pressure. However, persons with a higher cellular Ca2+ turnover rate show a greater susceptibility for an increase in the cellular Ca2+ load on a high salt diet than persons with a relatively low cellular Ca2+ turnover rate. In individuals who are salt sensitive, the increase in the Ca2+ load due to a high salt diet is expressed by a rise in the freely exchangeable Ca2+ (FECa2+) in the sarco(endo)plasmic reticulum (SER), coupled with the upregulation of the function and protein expression of the SER Ca2+-ATPase (SERCA). To test this hypothesis, the activities of SOCC and the Na+/Ca2+ exchanger will be characterized in platelets and lymphocytes of men and women on high and low dietary sodium intakes. The cellular Ca2+ turnover rate will be evaluated as a predictor of cellular and systemic responses to transition from high to low salt diets. The following responses to dietary sodium manipulation will be monitored: a)2+ change in the FECa in the dense tubules of platelets and in the SER of lymphocytes, b) parameters of SERCA kinetics, c) the protein expressions of SERCA 2b and 3 isoforms, d) blood pressure, e) parameters of the pressure natriuresis curve, and f) renal functions. Experiments will be performed both in outpatient and inpatient settings. The investigators state that the results of the study will generate a novel perspective about phenotypes of salt sensitivity and, an insight into the cardiovascular effects of high salt in humans.
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